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Papers by Judy Cameron

Research paper thumbnail of Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, Jan 13, 2018

Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differ... more Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (sh...

Research paper thumbnail of Influence of Nutrition on the Hypothalamic-Pituitary-Gonadal Axis in Primates

The Menstrual Cycle and Its Disorders

Research paper thumbnail of Long-lasting effect of obesity on skeletal muscle transcriptome

BMC genomics, May 25, 2017

Reduced physical activity and increased intake of calorically-dense diets are the main risk facto... more Reduced physical activity and increased intake of calorically-dense diets are the main risk factors for obesity, glucose intolerance, and type 2 diabetes. Chronic overnutrition and hyperglycemia can alter gene expression, contributing to long-term obesity complications. While caloric restriction can reduce obesity and glucose intolerance, it is currently unknown whether it can effectively reprogram transcriptome to a pre-obesity level. The present study addressed this question by the preliminary examination of the transcriptional dynamics in skeletal muscle after exposure to overnutrition and following caloric restriction. Six male rhesus macaques of 12-13 years of age consumed a high-fat western-style diet for 6 months and then were calorically restricted for 4 months without exercise. Skeletal muscle biopsies were subjected to longitudinal gene expression analysis using next-generation whole-genome RNA sequencing. In spite of significant weight loss and normalized insulin sensitiv...

Research paper thumbnail of Maternal deprivation alters expression of neural maturation gene tbr1 in the amygdala paralaminar nucleus in infant female macaques

Developmental psychobiology, Mar 4, 2016

Early parental loss is associated with social-emotional dysregulation and amygdala physiologic ch... more Early parental loss is associated with social-emotional dysregulation and amygdala physiologic changes. Previously, we examined whole amygdala gene expression in infant monkeys exposed to early maternal deprivation. Here, we focus on an amygdala region with immature neurons at birth: the paralaminar nucleus (PL). We hypothesized that 1) the normal infant PL is enriched in a subset of neural maturation (NM) genes compared to a nearby amygdala subregion; and 2) maternal deprivation would downregulate expression of NM transcripts (mRNA). mRNAs for bcl2, doublecortin, neuroD1, and tbr1-genes expressed in post-mitotic neurons-were enriched in the normal PL. Maternal deprivation at either 1 week or 1 month of age resulted in PL-specific downregulation of tbr1-a transcription factor necessary for directing neuroblasts to a glutamatergic phenotype. tbr1 expression also correlated with typical social behaviors. We conclude that maternal deprivation influences glutamatergic neuronal developme...

Research paper thumbnail of Pattern of Oxytocin Concentrations in the Plasma and Cerebrospinal Fluid of Lactating Rhesus Monkeys (Macaca mulatto,): Evidence for Functionally Independent Oxytocinergic Pathways in Primates

J Clin Endocrinol Metab, 1990

Two populations of oxytocin-staining neurons have been identified in the paraventricular nucleus:... more Two populations of oxytocin-staining neurons have been identified in the paraventricular nucleus: magnocellular neurons that terminate in the posterior pituitary and parvocellular neurons that terminate elsewhere in the central nervous system. Whether these oxytocin neurons are functionally separate was tested by measuring oxytocin concentrations in samples of peripheral blood and cerebrospinal fluid (CSF) obtained simultaneously from lactating rhesus monkeys during suckling. Lactating animals bearing temporary subarachnoid and venous catheters were maintained in a constant photoperiod (0600-1800 h). Samples of CSF were continuously withdrawn by peristaltic pump (0.1 mL/15 min) for 2-4 consecutive days from subarachnoid catheters with the tips placed at the T12-L1 level of the spinal column in four lactating monkeys 4 months postpartum and again after weaning. On 2 of these days, we observed and recorded periods of infant suckling and collected peripheral blood samples (1.2 mL) from the mother at 5-min intervals for 60 min. Oxytocin was measured in blood and CSF by RIA. Oxytocin concentrations increased in the plasma of the lactating monkeys during periods of nursing, with peak concentrations ranging from 4-16.7 microU/mL. No increase in plasma oxytocin was found on the day after the infant was weaned. Variations in the concentrations of oxytocin in CSF were independent of the suckling stimulus and plasma oxytocin concentrations and occurred during observed periods of no nipple contact by the infant and at the time of weaning after the infant had been removed from the mother. Each lactating animal also displayed a normal circadian variation in CSF oxytocin concentrations, with peak and nadir levels during light and dark hours, respectively. We conclude that release of oxytocin into the CSF of lactating monkeys is disassociated from release into the peripheral circulation. The data further support the conclusion that neuronal pathways giving rise to oxytocin in the CSF and the periphery are anatomically and functionally separate in primates.

Research paper thumbnail of Orcadian Rhythm of Oxytocin in the Cerebrospinal Fluid of Rhesus and Cynomolgus Monkeys: Effects of Castration and Adrenalectomy and Presence of a Caudal-Rostral Gradient

Neuroendocrinology, 1989

Oxytocin and vasopressin (AVP) were previously reported to have a diurnal rhythm in cerebrospinal... more Oxytocin and vasopressin (AVP) were previously reported to have a diurnal rhythm in cerebrospinal fluid (CSF) collected from the cervical cistern of chaired, intact male rhesus monkeys. In the present study, we continuously sampled CSF from temporary indwelling catheters placed in the spinal subarachnoid space of unanesthetized monkeys maintained on tether and swivel systems. CSF was collected from intact and castrate female rhesus monkeys and intact female and castrate, adrenalectomized male cynomolgus monkeys to determine if oxytocin and AVP rhythms are expressed in spinal subarachnoid CSF, if the magnitude of the CSF rhythm displays a rostral-caudal gradient, and if the rhythm is present in adrenalectomized and castrate monkeys, or is specific to the sex or species of macaque. Monkeys, maintained on a 12-hour light/dark cycle with lights on from 06.00 to 18.00 h, had 19-gauge epidural catheters introduced at the L4-L5 intervertebral space and advanced cephalad in the subarachnoid space. The proximal end of the catheter was connected to a peristaltic pump for continuous removal of CSF (0.5 ml/h) and hourly CSF samples were radioimmunoassayed for oxytocin and AVP. For rostral-caudal studies, the distal tip of the catheter was repositioned every few days to collect CSF from 3 levels of the spinal subarachnoid space: C5-6, T5-6, T12-L1. Each animal had a diurnal CSF oxytocin rhythm with peak and trough oxytocin levels during early light and dark periods, respectively. The magnitude of the oxytocin rhythm differed among animals, but was consistent in an animal from day to day.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Growth Hormone Response to Growth Hormone-Releasing Hormone and Clonidine in Young Monkeys: Correlation with Behavioral Characteristics

Journal of Child and Adolescent Psychopharmacology, Sep 1, 2003

Research paper thumbnail of Progress and Implications for Mental Health

Social neuroscience is a new, interdisciplinary field devoted to understanding how biological sys... more Social neuroscience is a new, interdisciplinary field devoted to understanding how biological systems implement social processes and behavior. Social neuroscience capitalizes on biological concepts and methods to inform and refine theories of social behavior, and it uses social and behavioral constructs and data to inform and refine theories of neural organization and function. We focus here on the progress and potential of social neuroscience in the area of mental health. Research in social neuroscience has grown dramatically in recent years. Among the most active areas of research we found are brain-imaging studies in normal children and adults; animal models of social behavior; studies of stroke patients; imaging studies of psychiatric patients; and research on social determinants of peripheral neural, neuroendocrine, and immunological processes. We also found that these areas of research are proceeding along largely independent trajectories. Our goals in this article are to review the development of this field, examine some currently promising approaches, identify obstacles and opportunities for future advances and integration, and consider how this research can inform work on the diagnosis and treatment of mental disorders.

Research paper thumbnail of The reproductive system and exercise in women

Medicine Amp Science in Sports Amp Exercise, 1992

Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... LOUCKS, ANNE B.; VAITUKAITIS, ...

Research paper thumbnail of A Primate Model of the Effects of Childhood Antidepressant Treatment

The American Journal of Psychiatry, Jan 31, 2014

Research paper thumbnail of Inhibition of Gonadotropin Secretion in Castrated Male Rhesus Monkeys (Macaca mulatto) Induced by Dietary Restriction: Analogy with the Prepubertal Hiatus of Gonadotropin Release

Endocrinology, 1986

The purpose of this study was to examine further the notion that in higher primates, analogous ne... more The purpose of this study was to examine further the notion that in higher primates, analogous neuroendocrine mechanisms may underlie the hiatus in LH and FSH secretion during prepubertal development and the suppression of gonadotropin release in adults during states of malnutrition. To this end, the metabolic sequelae and the gonadotropin response to restricted food intake (RFI) were determined in nine castrated male rhesus monkeys. The results obtained were then evaluated in light of current understanding of the neuroendocrine bases of the ontogeny of gonadotropin secretion in primates. A reduction in food intake from approximately 1150 Cal/day to approximately 200 Cal/day for 20-34 days resulted in declines in body weight and circulating LH and FSH concentrations. The reduction in body weight and the suppression of LH secretion were statistically significant (P less than 0.05). The decrease in gonadotropin secretion induced by RFI was fully restored by the chronic iv intermittent infusion of GnRH (0.1 microgram/min for 3 min every hour). These findings graphically demonstrate that RFI, or a sequelae of this nutritional perturbation, inhibits gonadotropin secretion, in the absence of feedback influences by gonadal hormones, by an action at a suprapituitary level that is mediated by interruption of intermittent hypothalamic GnRH discharge. The apparent arrest of the neural mechanism that governs the timing of intermittent GnRH discharge, the so-called GnRH pulse generator, was associated with decreases in plasma insulin (P = 0.078), T4 (P less than 0.05), and T3 (P less than 0.05) concentrations and with a significant (P less than 0.05) elevation in circulating cortisol levels. Although a general decrease in circulating amino acid levels was not observed during RFI, plasma glutamate concentrations were significantly (P less than 0.05) reduced by the nutritional perturbation. RFI resulted in unremarkable hypoglycemia. While the suppression of gonadotropin secretion in castrated male monkeys during RFI resembled, in certain aspects, the hiatus in gonadotropin secretion during prepubertal development, the endocrine and metabolic concomitants of these two physiological states exhibited important differences. Thus, the contemporary notion that the study of dietary restriction in adult primates may provide insights into the neuroendocrine mechanisms that govern the timing of the onset of puberty in these species should not be accepted without careful consideration.

Research paper thumbnail of Anxious behavior and fenfluramine-induced prolactin secretion in young rhesus macaques with different alleles of the serotonin reuptake transporter polymorphism (5HTTTLPR)

Behavior Genetics, 2004

Anxiety is a normal aspect of human personality, which can manifest in a variety of disorders and... more Anxiety is a normal aspect of human personality, which can manifest in a variety of disorders and other negative traits. The primary treatment for anxiety is the class of drugs known as the selective serotonin reuptake inhibitors (SSRIs), which bind to the serotonin reuptake transporter. The upstream region of the gene that codes for this transporter contains a polymorphism that is an insertion/deletion event that in turn, produces long (l) and short (s) alleles in the population. This particular polymorphism in the serotonin transporter, the 5HTTLPR (serotonin transporter linked polymorphic region), is thought to be involved in the genesis of anxious traits and disorders. Most studies with human subjects have examined adult behavior, which may derive from diverse experiential and environmental backgrounds, as well as genetic differences. To better isolate the effect of genetics, we genotyped 128 infant and juvenile monkeys for the 5HTTLPR and tested for behavioral response in four testing paradigms designed to elicit fearful-anxious behaviors: a free play, remote-controlled car, human intruder, and novel fruit test. The s͞s monkeys were found to be behaviorally inhibited in the free play test, engaged in more fear behaviors in the remote-controlled car test, and threatened more in the stare portion of the human intruder test, even though a small number of monkeys were assessed. There was no difference between genotypes of either sex in the prolactin response to fenfluramine. These data indicate greater anxiety in the s͞s monkeys for distinct facets of anxious behavior, which are independent of a global neurohormonal challenge test. These neurobehavioral data support recent neuroimaging findings in humans indicating the importance of the 5HTTLPR for amygdaladependent anxious behavior.

Research paper thumbnail of Oxytocin and vasopressin secretion in monkeys administered apomorphine and A D2 receptor agonist

Life Sci, 1993

Nauseogenic agents, such as apomorphine, were previously reported to promote peripheral release o... more Nauseogenic agents, such as apomorphine, were previously reported to promote peripheral release of oxytocin (OT), but not vasopressin (AVP) in rats, and AVP, but not OT in humans (7-13). In the present study, we compared the peripheral secretory responses of OT and AVP in adult male and female rhesus and male cynomolgus monkeys administered graded doses of apomorphine and the respective dopamine D1 and D2 receptor agonists, CY 208-243 and LY 163502. Apomorphine (50-400 micrograms/kg) and LY 163502 (10-100 micrograms/kg) elicited dose-dependent stimulation of OT and AVP, whereas CY 208-243 did not significantly increase secretion of either hormone. The magnitude of the OT and AVP secretory response varied among the animals. Peripheral OT and AVP responses were robust, but the magnitude of the secretory responses was greater for AVP than OT. None of the animals displayed emetic behavior during the studies. These studies indicate that dopaminergic stimulation, particularly of D2 receptors, can regulate both AVP and OT secretion in monkeys.

Research paper thumbnail of A Western-style diet, with and without chronic androgen treatment, alters the number, structure, and function of small antral follicles in ovaries of young adult monkeys

Fertility and sterility, Jan 21, 2015

To examine the small antral follicle (SAF) cohort in ovaries of adult rhesus monkeys after consum... more To examine the small antral follicle (SAF) cohort in ovaries of adult rhesus monkeys after consumption of a Western-style diet (WSD), with or without chronically elevated androgen levels since before puberty. Cholesterol or T (n = 6 per group) implants were placed SC in female rhesus macaques beginning at 1 year of age (prepubertal), with addition of a WSD (high fat/fructose) at 5.5 years (menarche approximately 2.6 years). Ovaries were collected at 7 years of age. One ovary per female was embedded in paraffin for morphologic and immunohistochemical analyses. The SAFs (<2.5 mm) were dissected from the other ovary obtained at or near menses in a subgroup of females (n = 3 per group) and processed for microarray analyses of the SAF transcriptome. Ovaries of adult monkeys consuming a standard macaque diet (low in fats and sugars) were obtained at similar stages of the menstrual cycle and used as controls for all analyses. Primate research center. Adult, female rhesus monkeys (Macaca...

Research paper thumbnail of Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys

Hormone Research in Paediatrics, Feb 1, 1992

Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to deter... more Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates.

Research paper thumbnail of Pattern of oxytocin concentration in the plasma and cerebrospinal fluid of lactating rhesus monkeys (Macaca mulatta) : evidence for functionally independent oxytocinergic pathways in primates

The Journal of Clinical Endocrinology and Metabolism, 1990

Research paper thumbnail of The Importance of Early Life Experience on Lifelong Emotion Regulation

Research paper thumbnail of Cerebrospinal fluid concentrations of tryptophan and 5-hydroxyindoleacetic acid in Macaca mulatta: diurnal variations and response to chronic changes in dietary protein intake

Neurochemical research, 2000

In rats, dietary protein is known to influence brain tryptophan (TRP) concentrations and serotoni... more In rats, dietary protein is known to influence brain tryptophan (TRP) concentrations and serotonin (5HT) synthesis. However, few studies have examined this relationship in primates (including humans). We therefore studied the effect in monkeys of changes in chronic protein intake on plasma and cerebrospinal fluid (CSF) concentrations of TRP and 5-hydroxyindoleacetic acid (5HIAA), the principal 5HT metabolite. Juvenile male monkeys (Macacca mulatta) consumed for sequential 4-week periods diets differing in protein content (approximately 23%-->approximately 16%--> approximately 10%-->approximately 6% protein [%-energy/day]). Each day, food was presented as a morning meal of fruit, and an afternoon meal consisting of a pelleted, commercial diet and fruit. During week 4 on each diet, blood and CSF were sampled diurnally via indwelling catheters. Plasma and CSF TRP varied diurnally and with dietary protein content. On all diets, CSF TRP declined modestly in the morning, and incr...

Research paper thumbnail of Neurorestoration by physical exercise: moving forward

Parkinsonism & related disorders, 2012

Although a good deal is known about the pathophysiology of Parkinson's disease and informatio... more Although a good deal is known about the pathophysiology of Parkinson's disease and information is emerging about its cause, there are no pharmacological treatments shown to have a significant, sustained capacity to prevent or attenuate the condition. However, accumulating clinical evidence suggests that physical exercise can provide this much needed treatment, and studies of animal models of the dopamine deficiency associated with the motor symptoms of Parkinson's disease further support this hypothesis. Thus, in our collaborative research efforts, we seek to understand the biological basis for exercise-induced protection in order to assist in the development of a safe and clinically effective intervention based on increased physical activity. In addition, we recognize that some individuals cannot or will not engage in physical exercise, and believe that mechanistic studies of exercise-induced protection will provide insights into the development of drugs that could emulate ...

Research paper thumbnail of Serotonin-related gene expression in female monkeys with individual sensitivity to stress

Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate met... more Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. In this study, the expression of four genes pivotal to serotonin neural function was assessed in monkeys previously categorized as highly stress resistant (n‫;3؍‬ normal menstrual cyclicity through two stress cycles), medium stress resistant (n‫;5؍‬ ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e. stress-sensitive; n‫;4؍‬ anovulatory as soon as stress is initiated). In situ hybridization and quantitative image analysis was used to measure mRNAs coding for SERT (serotonin transporter), 5HT1A autoreceptor, MAO-A and MAO-B (monoamine oxidases) at six levels of the dorsal raphe nucleus (DRN). Optical density (OD) and positive pixel area were measured with NIH Image software. In addition, serotonin neurons were immunostained and counted at three levels of the DRN. Finally, each animal was genotyped for the serotonin transporter long polymorphic region (5HTTLPR). Stress sensitive animals had lower expression of SERT mRNA in the caudal region of the DRN (P<0.04). SERT mRNA OD in the caudal DRN was positively correlated with serum progesterone during a pre-stress control cycle (P<0.0007). 5HT1A mRNA OD signal tended to decline in the stress-sensitive group, but statistical difference between averages was lacking in analysis of variance. However, 5HT1A mRNA signal was positively correlated with control cycle progesterone (P<0.009). There was significantly less MAO-A mRNA signal in the stress-sensitive group (P<0.007) and MAO-A OD was positively correlated with progesterone from a pre-stress control cycle (P<0.007). MAO-B mRNA exhibited a similar downward trend in the stress-sensitive group. MAO-B OD also correlated with control cycle progesterone (P<0.003). There were significantly fewer serotonin neurons in the stress-sensitive group. All animals contained only the long form of the 5HTTLPR. Thus, all serotonin-related mRNAs examined in the dorsal raphe to date were lower (SERT, MAO-A) or exhibited a lower trend (5HT1A, MAO-B) in the stress sensitive animals, which probably reflects the lower number of serotonin neurons present.

Research paper thumbnail of Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, Jan 13, 2018

Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differ... more Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (sh...

Research paper thumbnail of Influence of Nutrition on the Hypothalamic-Pituitary-Gonadal Axis in Primates

The Menstrual Cycle and Its Disorders

Research paper thumbnail of Long-lasting effect of obesity on skeletal muscle transcriptome

BMC genomics, May 25, 2017

Reduced physical activity and increased intake of calorically-dense diets are the main risk facto... more Reduced physical activity and increased intake of calorically-dense diets are the main risk factors for obesity, glucose intolerance, and type 2 diabetes. Chronic overnutrition and hyperglycemia can alter gene expression, contributing to long-term obesity complications. While caloric restriction can reduce obesity and glucose intolerance, it is currently unknown whether it can effectively reprogram transcriptome to a pre-obesity level. The present study addressed this question by the preliminary examination of the transcriptional dynamics in skeletal muscle after exposure to overnutrition and following caloric restriction. Six male rhesus macaques of 12-13 years of age consumed a high-fat western-style diet for 6 months and then were calorically restricted for 4 months without exercise. Skeletal muscle biopsies were subjected to longitudinal gene expression analysis using next-generation whole-genome RNA sequencing. In spite of significant weight loss and normalized insulin sensitiv...

Research paper thumbnail of Maternal deprivation alters expression of neural maturation gene tbr1 in the amygdala paralaminar nucleus in infant female macaques

Developmental psychobiology, Mar 4, 2016

Early parental loss is associated with social-emotional dysregulation and amygdala physiologic ch... more Early parental loss is associated with social-emotional dysregulation and amygdala physiologic changes. Previously, we examined whole amygdala gene expression in infant monkeys exposed to early maternal deprivation. Here, we focus on an amygdala region with immature neurons at birth: the paralaminar nucleus (PL). We hypothesized that 1) the normal infant PL is enriched in a subset of neural maturation (NM) genes compared to a nearby amygdala subregion; and 2) maternal deprivation would downregulate expression of NM transcripts (mRNA). mRNAs for bcl2, doublecortin, neuroD1, and tbr1-genes expressed in post-mitotic neurons-were enriched in the normal PL. Maternal deprivation at either 1 week or 1 month of age resulted in PL-specific downregulation of tbr1-a transcription factor necessary for directing neuroblasts to a glutamatergic phenotype. tbr1 expression also correlated with typical social behaviors. We conclude that maternal deprivation influences glutamatergic neuronal developme...

Research paper thumbnail of Pattern of Oxytocin Concentrations in the Plasma and Cerebrospinal Fluid of Lactating Rhesus Monkeys (Macaca mulatto,): Evidence for Functionally Independent Oxytocinergic Pathways in Primates

J Clin Endocrinol Metab, 1990

Two populations of oxytocin-staining neurons have been identified in the paraventricular nucleus:... more Two populations of oxytocin-staining neurons have been identified in the paraventricular nucleus: magnocellular neurons that terminate in the posterior pituitary and parvocellular neurons that terminate elsewhere in the central nervous system. Whether these oxytocin neurons are functionally separate was tested by measuring oxytocin concentrations in samples of peripheral blood and cerebrospinal fluid (CSF) obtained simultaneously from lactating rhesus monkeys during suckling. Lactating animals bearing temporary subarachnoid and venous catheters were maintained in a constant photoperiod (0600-1800 h). Samples of CSF were continuously withdrawn by peristaltic pump (0.1 mL/15 min) for 2-4 consecutive days from subarachnoid catheters with the tips placed at the T12-L1 level of the spinal column in four lactating monkeys 4 months postpartum and again after weaning. On 2 of these days, we observed and recorded periods of infant suckling and collected peripheral blood samples (1.2 mL) from the mother at 5-min intervals for 60 min. Oxytocin was measured in blood and CSF by RIA. Oxytocin concentrations increased in the plasma of the lactating monkeys during periods of nursing, with peak concentrations ranging from 4-16.7 microU/mL. No increase in plasma oxytocin was found on the day after the infant was weaned. Variations in the concentrations of oxytocin in CSF were independent of the suckling stimulus and plasma oxytocin concentrations and occurred during observed periods of no nipple contact by the infant and at the time of weaning after the infant had been removed from the mother. Each lactating animal also displayed a normal circadian variation in CSF oxytocin concentrations, with peak and nadir levels during light and dark hours, respectively. We conclude that release of oxytocin into the CSF of lactating monkeys is disassociated from release into the peripheral circulation. The data further support the conclusion that neuronal pathways giving rise to oxytocin in the CSF and the periphery are anatomically and functionally separate in primates.

Research paper thumbnail of Orcadian Rhythm of Oxytocin in the Cerebrospinal Fluid of Rhesus and Cynomolgus Monkeys: Effects of Castration and Adrenalectomy and Presence of a Caudal-Rostral Gradient

Neuroendocrinology, 1989

Oxytocin and vasopressin (AVP) were previously reported to have a diurnal rhythm in cerebrospinal... more Oxytocin and vasopressin (AVP) were previously reported to have a diurnal rhythm in cerebrospinal fluid (CSF) collected from the cervical cistern of chaired, intact male rhesus monkeys. In the present study, we continuously sampled CSF from temporary indwelling catheters placed in the spinal subarachnoid space of unanesthetized monkeys maintained on tether and swivel systems. CSF was collected from intact and castrate female rhesus monkeys and intact female and castrate, adrenalectomized male cynomolgus monkeys to determine if oxytocin and AVP rhythms are expressed in spinal subarachnoid CSF, if the magnitude of the CSF rhythm displays a rostral-caudal gradient, and if the rhythm is present in adrenalectomized and castrate monkeys, or is specific to the sex or species of macaque. Monkeys, maintained on a 12-hour light/dark cycle with lights on from 06.00 to 18.00 h, had 19-gauge epidural catheters introduced at the L4-L5 intervertebral space and advanced cephalad in the subarachnoid space. The proximal end of the catheter was connected to a peristaltic pump for continuous removal of CSF (0.5 ml/h) and hourly CSF samples were radioimmunoassayed for oxytocin and AVP. For rostral-caudal studies, the distal tip of the catheter was repositioned every few days to collect CSF from 3 levels of the spinal subarachnoid space: C5-6, T5-6, T12-L1. Each animal had a diurnal CSF oxytocin rhythm with peak and trough oxytocin levels during early light and dark periods, respectively. The magnitude of the oxytocin rhythm differed among animals, but was consistent in an animal from day to day.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Growth Hormone Response to Growth Hormone-Releasing Hormone and Clonidine in Young Monkeys: Correlation with Behavioral Characteristics

Journal of Child and Adolescent Psychopharmacology, Sep 1, 2003

Research paper thumbnail of Progress and Implications for Mental Health

Social neuroscience is a new, interdisciplinary field devoted to understanding how biological sys... more Social neuroscience is a new, interdisciplinary field devoted to understanding how biological systems implement social processes and behavior. Social neuroscience capitalizes on biological concepts and methods to inform and refine theories of social behavior, and it uses social and behavioral constructs and data to inform and refine theories of neural organization and function. We focus here on the progress and potential of social neuroscience in the area of mental health. Research in social neuroscience has grown dramatically in recent years. Among the most active areas of research we found are brain-imaging studies in normal children and adults; animal models of social behavior; studies of stroke patients; imaging studies of psychiatric patients; and research on social determinants of peripheral neural, neuroendocrine, and immunological processes. We also found that these areas of research are proceeding along largely independent trajectories. Our goals in this article are to review the development of this field, examine some currently promising approaches, identify obstacles and opportunities for future advances and integration, and consider how this research can inform work on the diagnosis and treatment of mental disorders.

Research paper thumbnail of The reproductive system and exercise in women

Medicine Amp Science in Sports Amp Exercise, 1992

Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... LOUCKS, ANNE B.; VAITUKAITIS, ...

Research paper thumbnail of A Primate Model of the Effects of Childhood Antidepressant Treatment

The American Journal of Psychiatry, Jan 31, 2014

Research paper thumbnail of Inhibition of Gonadotropin Secretion in Castrated Male Rhesus Monkeys (Macaca mulatto) Induced by Dietary Restriction: Analogy with the Prepubertal Hiatus of Gonadotropin Release

Endocrinology, 1986

The purpose of this study was to examine further the notion that in higher primates, analogous ne... more The purpose of this study was to examine further the notion that in higher primates, analogous neuroendocrine mechanisms may underlie the hiatus in LH and FSH secretion during prepubertal development and the suppression of gonadotropin release in adults during states of malnutrition. To this end, the metabolic sequelae and the gonadotropin response to restricted food intake (RFI) were determined in nine castrated male rhesus monkeys. The results obtained were then evaluated in light of current understanding of the neuroendocrine bases of the ontogeny of gonadotropin secretion in primates. A reduction in food intake from approximately 1150 Cal/day to approximately 200 Cal/day for 20-34 days resulted in declines in body weight and circulating LH and FSH concentrations. The reduction in body weight and the suppression of LH secretion were statistically significant (P less than 0.05). The decrease in gonadotropin secretion induced by RFI was fully restored by the chronic iv intermittent infusion of GnRH (0.1 microgram/min for 3 min every hour). These findings graphically demonstrate that RFI, or a sequelae of this nutritional perturbation, inhibits gonadotropin secretion, in the absence of feedback influences by gonadal hormones, by an action at a suprapituitary level that is mediated by interruption of intermittent hypothalamic GnRH discharge. The apparent arrest of the neural mechanism that governs the timing of intermittent GnRH discharge, the so-called GnRH pulse generator, was associated with decreases in plasma insulin (P = 0.078), T4 (P less than 0.05), and T3 (P less than 0.05) concentrations and with a significant (P less than 0.05) elevation in circulating cortisol levels. Although a general decrease in circulating amino acid levels was not observed during RFI, plasma glutamate concentrations were significantly (P less than 0.05) reduced by the nutritional perturbation. RFI resulted in unremarkable hypoglycemia. While the suppression of gonadotropin secretion in castrated male monkeys during RFI resembled, in certain aspects, the hiatus in gonadotropin secretion during prepubertal development, the endocrine and metabolic concomitants of these two physiological states exhibited important differences. Thus, the contemporary notion that the study of dietary restriction in adult primates may provide insights into the neuroendocrine mechanisms that govern the timing of the onset of puberty in these species should not be accepted without careful consideration.

Research paper thumbnail of Anxious behavior and fenfluramine-induced prolactin secretion in young rhesus macaques with different alleles of the serotonin reuptake transporter polymorphism (5HTTTLPR)

Behavior Genetics, 2004

Anxiety is a normal aspect of human personality, which can manifest in a variety of disorders and... more Anxiety is a normal aspect of human personality, which can manifest in a variety of disorders and other negative traits. The primary treatment for anxiety is the class of drugs known as the selective serotonin reuptake inhibitors (SSRIs), which bind to the serotonin reuptake transporter. The upstream region of the gene that codes for this transporter contains a polymorphism that is an insertion/deletion event that in turn, produces long (l) and short (s) alleles in the population. This particular polymorphism in the serotonin transporter, the 5HTTLPR (serotonin transporter linked polymorphic region), is thought to be involved in the genesis of anxious traits and disorders. Most studies with human subjects have examined adult behavior, which may derive from diverse experiential and environmental backgrounds, as well as genetic differences. To better isolate the effect of genetics, we genotyped 128 infant and juvenile monkeys for the 5HTTLPR and tested for behavioral response in four testing paradigms designed to elicit fearful-anxious behaviors: a free play, remote-controlled car, human intruder, and novel fruit test. The s͞s monkeys were found to be behaviorally inhibited in the free play test, engaged in more fear behaviors in the remote-controlled car test, and threatened more in the stare portion of the human intruder test, even though a small number of monkeys were assessed. There was no difference between genotypes of either sex in the prolactin response to fenfluramine. These data indicate greater anxiety in the s͞s monkeys for distinct facets of anxious behavior, which are independent of a global neurohormonal challenge test. These neurobehavioral data support recent neuroimaging findings in humans indicating the importance of the 5HTTLPR for amygdaladependent anxious behavior.

Research paper thumbnail of Oxytocin and vasopressin secretion in monkeys administered apomorphine and A D2 receptor agonist

Life Sci, 1993

Nauseogenic agents, such as apomorphine, were previously reported to promote peripheral release o... more Nauseogenic agents, such as apomorphine, were previously reported to promote peripheral release of oxytocin (OT), but not vasopressin (AVP) in rats, and AVP, but not OT in humans (7-13). In the present study, we compared the peripheral secretory responses of OT and AVP in adult male and female rhesus and male cynomolgus monkeys administered graded doses of apomorphine and the respective dopamine D1 and D2 receptor agonists, CY 208-243 and LY 163502. Apomorphine (50-400 micrograms/kg) and LY 163502 (10-100 micrograms/kg) elicited dose-dependent stimulation of OT and AVP, whereas CY 208-243 did not significantly increase secretion of either hormone. The magnitude of the OT and AVP secretory response varied among the animals. Peripheral OT and AVP responses were robust, but the magnitude of the secretory responses was greater for AVP than OT. None of the animals displayed emetic behavior during the studies. These studies indicate that dopaminergic stimulation, particularly of D2 receptors, can regulate both AVP and OT secretion in monkeys.

Research paper thumbnail of A Western-style diet, with and without chronic androgen treatment, alters the number, structure, and function of small antral follicles in ovaries of young adult monkeys

Fertility and sterility, Jan 21, 2015

To examine the small antral follicle (SAF) cohort in ovaries of adult rhesus monkeys after consum... more To examine the small antral follicle (SAF) cohort in ovaries of adult rhesus monkeys after consumption of a Western-style diet (WSD), with or without chronically elevated androgen levels since before puberty. Cholesterol or T (n = 6 per group) implants were placed SC in female rhesus macaques beginning at 1 year of age (prepubertal), with addition of a WSD (high fat/fructose) at 5.5 years (menarche approximately 2.6 years). Ovaries were collected at 7 years of age. One ovary per female was embedded in paraffin for morphologic and immunohistochemical analyses. The SAFs (<2.5 mm) were dissected from the other ovary obtained at or near menses in a subgroup of females (n = 3 per group) and processed for microarray analyses of the SAF transcriptome. Ovaries of adult monkeys consuming a standard macaque diet (low in fats and sugars) were obtained at similar stages of the menstrual cycle and used as controls for all analyses. Primate research center. Adult, female rhesus monkeys (Macaca...

Research paper thumbnail of Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys

Hormone Research in Paediatrics, Feb 1, 1992

Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to deter... more Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates.

Research paper thumbnail of Pattern of oxytocin concentration in the plasma and cerebrospinal fluid of lactating rhesus monkeys (Macaca mulatta) : evidence for functionally independent oxytocinergic pathways in primates

The Journal of Clinical Endocrinology and Metabolism, 1990

Research paper thumbnail of The Importance of Early Life Experience on Lifelong Emotion Regulation

Research paper thumbnail of Cerebrospinal fluid concentrations of tryptophan and 5-hydroxyindoleacetic acid in Macaca mulatta: diurnal variations and response to chronic changes in dietary protein intake

Neurochemical research, 2000

In rats, dietary protein is known to influence brain tryptophan (TRP) concentrations and serotoni... more In rats, dietary protein is known to influence brain tryptophan (TRP) concentrations and serotonin (5HT) synthesis. However, few studies have examined this relationship in primates (including humans). We therefore studied the effect in monkeys of changes in chronic protein intake on plasma and cerebrospinal fluid (CSF) concentrations of TRP and 5-hydroxyindoleacetic acid (5HIAA), the principal 5HT metabolite. Juvenile male monkeys (Macacca mulatta) consumed for sequential 4-week periods diets differing in protein content (approximately 23%-->approximately 16%--> approximately 10%-->approximately 6% protein [%-energy/day]). Each day, food was presented as a morning meal of fruit, and an afternoon meal consisting of a pelleted, commercial diet and fruit. During week 4 on each diet, blood and CSF were sampled diurnally via indwelling catheters. Plasma and CSF TRP varied diurnally and with dietary protein content. On all diets, CSF TRP declined modestly in the morning, and incr...

Research paper thumbnail of Neurorestoration by physical exercise: moving forward

Parkinsonism & related disorders, 2012

Although a good deal is known about the pathophysiology of Parkinson's disease and informatio... more Although a good deal is known about the pathophysiology of Parkinson's disease and information is emerging about its cause, there are no pharmacological treatments shown to have a significant, sustained capacity to prevent or attenuate the condition. However, accumulating clinical evidence suggests that physical exercise can provide this much needed treatment, and studies of animal models of the dopamine deficiency associated with the motor symptoms of Parkinson's disease further support this hypothesis. Thus, in our collaborative research efforts, we seek to understand the biological basis for exercise-induced protection in order to assist in the development of a safe and clinically effective intervention based on increased physical activity. In addition, we recognize that some individuals cannot or will not engage in physical exercise, and believe that mechanistic studies of exercise-induced protection will provide insights into the development of drugs that could emulate ...

Research paper thumbnail of Serotonin-related gene expression in female monkeys with individual sensitivity to stress

Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate met... more Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. In this study, the expression of four genes pivotal to serotonin neural function was assessed in monkeys previously categorized as highly stress resistant (n‫;3؍‬ normal menstrual cyclicity through two stress cycles), medium stress resistant (n‫;5؍‬ ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e. stress-sensitive; n‫;4؍‬ anovulatory as soon as stress is initiated). In situ hybridization and quantitative image analysis was used to measure mRNAs coding for SERT (serotonin transporter), 5HT1A autoreceptor, MAO-A and MAO-B (monoamine oxidases) at six levels of the dorsal raphe nucleus (DRN). Optical density (OD) and positive pixel area were measured with NIH Image software. In addition, serotonin neurons were immunostained and counted at three levels of the DRN. Finally, each animal was genotyped for the serotonin transporter long polymorphic region (5HTTLPR). Stress sensitive animals had lower expression of SERT mRNA in the caudal region of the DRN (P<0.04). SERT mRNA OD in the caudal DRN was positively correlated with serum progesterone during a pre-stress control cycle (P<0.0007). 5HT1A mRNA OD signal tended to decline in the stress-sensitive group, but statistical difference between averages was lacking in analysis of variance. However, 5HT1A mRNA signal was positively correlated with control cycle progesterone (P<0.009). There was significantly less MAO-A mRNA signal in the stress-sensitive group (P<0.007) and MAO-A OD was positively correlated with progesterone from a pre-stress control cycle (P<0.007). MAO-B mRNA exhibited a similar downward trend in the stress-sensitive group. MAO-B OD also correlated with control cycle progesterone (P<0.003). There were significantly fewer serotonin neurons in the stress-sensitive group. All animals contained only the long form of the 5HTTLPR. Thus, all serotonin-related mRNAs examined in the dorsal raphe to date were lower (SERT, MAO-A) or exhibited a lower trend (5HT1A, MAO-B) in the stress sensitive animals, which probably reflects the lower number of serotonin neurons present.