JR Galler - Academia.edu (original) (raw)

Papers by JR Galler

Research paper thumbnail of Impaired Response of Serum IGF-I Levels to Puberty in Previously Malnourished Adolescents

Nutritional Neuroscience, 1999

ABSTRACT

Research paper thumbnail of Prenatal Protein Malnutrition in Rats Enhances Serotonin Release from Hippocampus

The Journal of Nutrition, 1992

The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- ... more The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- to 240-d-old male rats. The malnourished rats (denoted 6,25 group) were males born to dams fed a 6% casein diet during pregnancy and fostered at birth to dams fed a control (25% casein) diet. They were compared with males born to dams fed 25% casein diet. Tissue concentrations of serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, L-tryptophan and catecholamines in the hippocampal formation in the 6,25 group were similar to those of well-fed controls (25,25 group). However, a twofold greater basal serotonin efflux from hippocampal slices of 6,25 rats compared with slices from 25,25 rats was observed during a 20-min incubation period. Hippocampal [3H]paroxetine binding indicated that there was no alteration of apparent maximal binding and affinity of the serotonin transporter in the 6,25 rats. In addition, there was no difference in serotonin receptor binding in hippocampal membranes from 6,25 and 25,25 rats. The results indicate that prenatal protein malnutrition causes selective changes in central serotonin metabolism.

Research paper thumbnail of Use of Partial Mammectomy to Produce Malnutrition in the Rat

Neonatology, 1977

Partial mammectomy in the Sprague-Dawley rat was studied as a method for producing malnutrition w... more Partial mammectomy in the Sprague-Dawley rat was studied as a method for producing malnutrition without accompanying differences in litter size. Throughout the litter period, experimental litters weighed less than controls. No difference in the rate of development of various anatomical landmarks was noted with this degree of malnutrition. Maternal behavior in the nursing dam was measured with respect to nursing, nesting, and retrieval behavior. Mammectomized subjects built and maintained better nests and spent more time in a nursing posture, but were less likely to retrieve their litter than were control animals. At weaning the intact mammae of the experimental animals were larger than those of control animals.

Research paper thumbnail of A Preliminary Study of Temperament Among Malnourished Mayan Children

Nutritional Neuroscience, 1998

Research paper thumbnail of Life-long effects of malnutrition using semi-quantitative EEG analysis

1ABSTRACTThe non-linear spatiotemporal features in the continuing EEG recordings could be helpful... more 1ABSTRACTThe non-linear spatiotemporal features in the continuing EEG recordings could be helpful to infer the physio and pathological significance of early insults on the brain, such as early malnutrition and their long-term effects. A unique opportunity is opened with the Barbados Nutrition Study (BNS) dedicated to studying Protein-Energy Malnutrition (PEM) with two groups, children suffering an early PEM episode and their controls. We evaluated the resting-state EEG (N=108, PEM=46) in 1978, and we repeated the EEG (N=97, PEM=46) in 2018. We did a qualitative analysis of the EEG using a semi-quantitative scale (Grand Total EEG (GTE)) and an item response theory (IRT) approach to estimate a latent variable that is able to explain the subjacent neurophysiological status (NPS). Finally, we applied a mixed-effects model with a sensitivity index for ignorability to test differences between the controls and PEM groups while accounting for the missing data mechanisms (nlme (Pinheiro J. 2...

Research paper thumbnail of A Follow-up Study of the Influence of Early Malnutrition on Development: V. Delayed Development of Conservation (Piaget)

Journal of the American Academy of Child & Adolescent Psychiatry, 1987

Research paper thumbnail of Prenatal protein malnutrition and maternal behavior in Sprague-Dawley rats

The Journal of nutrition, 1991

Research paper thumbnail of Variability of the effects of rearing in a large litter on the development of the rat

Developmental Psychobiology, 1975

Research paper thumbnail of Prenatal protein malnutrition alters behavioral state modulation of inhibition and facilitation in the dentate gyrus

Brain Research Bulletin, 1992

Research paper thumbnail of Long-term effects of early kwashiorkor compared with marasmus. II. Intellectual performance

Journal of pediatric …, 1987

Physical growth and sexual maturation were measured in a follow-up study of Barbadian girls and b... more Physical growth and sexual maturation were measured in a follow-up study of Barbadian girls and boys aged 11-18 years with histories of kwashiorkor (n = 54) or marasmus (n = 56) in their first year of life. They were compared with healthy neighborhood children matched by sex and age who had normal patterns of growth in early childhood (n = 59). Girls with histories of marasmus had significant delays in the onset of menarche compared with healthy comparison girls. However, their rate of growth during the previous 2 years was accelerated, and the differences in size were smaller than at the earlier testing, confirming catch-up. This pattern was not evident for girls with histories of kwashiorkor, who did not differ from the healthy comparison girls on either onset of menarche, Tanner ratings of sexual maturation, or measures of physical growth. In contrast, boys with histories of kwashiorkor or marasmus did not differ from healthy comparison boys in physical growth or Tanner ratings at these ages.

Research paper thumbnail of A preliminary study of temperament among malnourished Mayan children

Nutritional Neuroscience 1:141-149, 1998

Research paper thumbnail of Prenatally malnourished female but not male rats show increased sensitivity to MK-801 in a differential reinforcement of low rates task

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and c... more A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-depend...

Research paper thumbnail of The neural basis of attentional alterations in prenatally protein malnourished rats

Protein malnutrition during gestation alters brain development and produces specific behavioral a... more Protein malnutrition during gestation alters brain development and produces specific behavioral and cognitive changes that persist into adulthood and increase the risks of neuropsychiatric disorders. Given evidence for the role of the prefrontal cortex in such diseases, it is significant that studies in humans and animal models have shown that prenatal protein malnutrition specifically affects functions associated with prefrontal cortex. However, the neural basis underlying these changes is unclear. In the current study, prenatally malnourished and control rats performed a sustained attention task with an unpredictable distractor, a task that depends on intact prefrontal cortical function. Radiolabeled 2-deoxyglucose was used to measure neural and brain network activity during the task. Results confirmed that adult prenatally malnourished rats were more distractible than controls and exhibited lower functional activity in prefrontal cortices. Thus, prefrontal activity was a predicto...

Research paper thumbnail of Effect of Prenatal Protein Malnutrition on Birthdates and Number of Neurons in the Rat Locus Coeruleus

The effect of prenatal protein deprivation on the timing of neurogenesis and on the number of neu... more The effect of prenatal protein deprivation on the timing of neurogenesis and on the number of neurons generated in the locus coeruleus of the rat was studied. These neurons are of interest as their axon projections are involved in the earliest stages of cerebral cortical development. Dams were maintained on a 25% casein diet or a 6% casein diet five weeks prior to mating and the diets continued throughout the pregnancy. At birth, all pups were cross-fostered to dams on a 25% casein diet. BrDU, a thymidine analog that is incorporated into the nuclear DNA during the synthetic phase of the cell cycle, was used as a marker of the generation period. It was administered intraperitoneally (25 mg/kg body weight) on embryonic day 10, 11, 12, 13, or 14. On postnatal day 30, the brain stems were processed with BrDU immunocytochemistry to determine the relative number of neurons generated on each day, and with Nissl stain to determine the total number of neurons generated in the two groups. The...

Research paper thumbnail of The neural basis of attentional alterations in prenatally protein malnourished rats

Cerebral Cortex

Protein malnutrition during gestation alters brain development and produces specific behavioral a... more Protein malnutrition during gestation alters brain development and produces specific behavioral and cognitive changes that persist into adulthood and increase the risks of neuropsychiatric disorders. Given evidence for the role of the prefrontal cortex in such diseases, it is significant that studies in humans and animal models have shown that prenatal protein malnutrition specifically affects functions associated with prefrontal cortex. However, the neural basis underlying these changes is unclear. In the current study, prenatally malnourished and control rats performed a sustained attention task with an unpredictable distractor, a task that depends on intact prefrontal cortical function. Radiolabeled 2-deoxyglucose was used to measure neural and brain network activity during the task. Results confirmed that adult prenatally malnourished rats were more distractible than controls and exhibited lower functional activity in prefrontal cortices. Thus, prefrontal activity was a predicto...

Research paper thumbnail of Impact of early childhood malnutrition on the adult brain function: an ERP study

According to the World Health Organization, 45% of deaths among children under 5 years of age are... more According to the World Health Organization, 45% of deaths among children under 5 years of age are caused by childhood malnutrition, which affects 224 million children worldwide. The Barbados Nutrition Study (BNS) is a 50+year longitudinal study on a Barbadian cohort (N=258) with histories of moderate to severe protein-energy malnutrition (PEM) in the first year of life and healthy controls. Interestingly, a recent BNS publication used quantitative electroencephalography (EEG) to show differences in brain function (lower alpha1 activity and higher theta, alpha2 and beta activity) in children who suffered from early PEM compared to healthy controls. However, the adult brain function following early childhood PEM has not been reported in this cohort. In the current study, EEG recordings were undertaken during a Go-No-Go task on a subsample of the BNS cohort (n=55) at ages 45-51 years. Evoked-related potentials (ERP) analyses show that, compared to the control group (n=29), participants...

Research paper thumbnail of Prenatal protein level impacts homing behavior in Long-Evans rat pups

Nutritional neuroscience, Jan 20, 2015

Objective This study assessed the effect of varying prenatal protein levels on the development of... more Objective This study assessed the effect of varying prenatal protein levels on the development of homing orientation in rat pups. Methods Long-Evans rats were fed one of the four isocaloric diets containing 6% (n = 7 litters), 12% (n = 9), 18% (n = 9), or 25% (n = 10) casein prior to mating and throughout pregnancy. At birth, litters were fostered to well-nourished control mothers fed a 25% casein diet during pregnancy, and an adequate protein diet (25% casein) was provided to weaning. On postnatal days 5, 7, 9, 11, and 13, homing behaviors, including activity levels, rate of successful returns to the nest quadrant and latencies to reach the nest over a 3-minute test period were recorded from two starting positions in the home cage. Adult body and brain weights were obtained at sacrifice (postnatal day 130 or 200). Results Growth was impaired in pups whose mothers were fed a 6% or, to a lesser extent, a 12% casein diet relative to pups whose mothers were fed the 18 and 25% casein di...

Research paper thumbnail of Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex

Neuroscience, Jan 12, 2015

Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior includi... more Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in the PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with (14)C-2-deoxyglucose. Results showed decreased activation in the PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity.

Research paper thumbnail of Development and modulation of GABA(A) receptor-mediated neurotransmission in the CA1 region of prenatally protein malnourished rats

Nutritional neuroscience, 2001

Prenatal protein malnutrition has been demonstrated to result in alterations in the serotonergic ... more Prenatal protein malnutrition has been demonstrated to result in alterations in the serotonergic and GABAergic neurotransmitter systems in the rat hippocampus. In the present study, whole-cell patch clamp recordings of CA1 pyramidal cells were employed in an effort to gain insight into the specific cellular locus and functional consequences of the previously reported changes. Hippocampal slices were prepared from Sprague-Dawley rats whose dams were fed either a normal (25% casein) or low (6% casein) protein diet during pregnancy. The development of GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) and their modulation by the benzodiazipine agonist zolpidem were compared in cells from the two nutritional groups at postnatal days 7, 14, 21 and >90. The modulation of mIPSCs by serotonin was also examined in cells from 21 day old rats. No significant differences were observed in the characteristics of mIPSCs in cells from control vs. prenatally protein mal...

Research paper thumbnail of Prenatally malnourished female but not male rats show increased sensitivity to MK-801 in a differential reinforcement of low rates task

Behavioural pharmacology, 1998

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and c... more A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-depend...

Research paper thumbnail of Impaired Response of Serum IGF-I Levels to Puberty in Previously Malnourished Adolescents

Nutritional Neuroscience, 1999

ABSTRACT

Research paper thumbnail of Prenatal Protein Malnutrition in Rats Enhances Serotonin Release from Hippocampus

The Journal of Nutrition, 1992

The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- ... more The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- to 240-d-old male rats. The malnourished rats (denoted 6,25 group) were males born to dams fed a 6% casein diet during pregnancy and fostered at birth to dams fed a control (25% casein) diet. They were compared with males born to dams fed 25% casein diet. Tissue concentrations of serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, L-tryptophan and catecholamines in the hippocampal formation in the 6,25 group were similar to those of well-fed controls (25,25 group). However, a twofold greater basal serotonin efflux from hippocampal slices of 6,25 rats compared with slices from 25,25 rats was observed during a 20-min incubation period. Hippocampal [3H]paroxetine binding indicated that there was no alteration of apparent maximal binding and affinity of the serotonin transporter in the 6,25 rats. In addition, there was no difference in serotonin receptor binding in hippocampal membranes from 6,25 and 25,25 rats. The results indicate that prenatal protein malnutrition causes selective changes in central serotonin metabolism.

Research paper thumbnail of Use of Partial Mammectomy to Produce Malnutrition in the Rat

Neonatology, 1977

Partial mammectomy in the Sprague-Dawley rat was studied as a method for producing malnutrition w... more Partial mammectomy in the Sprague-Dawley rat was studied as a method for producing malnutrition without accompanying differences in litter size. Throughout the litter period, experimental litters weighed less than controls. No difference in the rate of development of various anatomical landmarks was noted with this degree of malnutrition. Maternal behavior in the nursing dam was measured with respect to nursing, nesting, and retrieval behavior. Mammectomized subjects built and maintained better nests and spent more time in a nursing posture, but were less likely to retrieve their litter than were control animals. At weaning the intact mammae of the experimental animals were larger than those of control animals.

Research paper thumbnail of A Preliminary Study of Temperament Among Malnourished Mayan Children

Nutritional Neuroscience, 1998

Research paper thumbnail of Life-long effects of malnutrition using semi-quantitative EEG analysis

1ABSTRACTThe non-linear spatiotemporal features in the continuing EEG recordings could be helpful... more 1ABSTRACTThe non-linear spatiotemporal features in the continuing EEG recordings could be helpful to infer the physio and pathological significance of early insults on the brain, such as early malnutrition and their long-term effects. A unique opportunity is opened with the Barbados Nutrition Study (BNS) dedicated to studying Protein-Energy Malnutrition (PEM) with two groups, children suffering an early PEM episode and their controls. We evaluated the resting-state EEG (N=108, PEM=46) in 1978, and we repeated the EEG (N=97, PEM=46) in 2018. We did a qualitative analysis of the EEG using a semi-quantitative scale (Grand Total EEG (GTE)) and an item response theory (IRT) approach to estimate a latent variable that is able to explain the subjacent neurophysiological status (NPS). Finally, we applied a mixed-effects model with a sensitivity index for ignorability to test differences between the controls and PEM groups while accounting for the missing data mechanisms (nlme (Pinheiro J. 2...

Research paper thumbnail of A Follow-up Study of the Influence of Early Malnutrition on Development: V. Delayed Development of Conservation (Piaget)

Journal of the American Academy of Child & Adolescent Psychiatry, 1987

Research paper thumbnail of Prenatal protein malnutrition and maternal behavior in Sprague-Dawley rats

The Journal of nutrition, 1991

Research paper thumbnail of Variability of the effects of rearing in a large litter on the development of the rat

Developmental Psychobiology, 1975

Research paper thumbnail of Prenatal protein malnutrition alters behavioral state modulation of inhibition and facilitation in the dentate gyrus

Brain Research Bulletin, 1992

Research paper thumbnail of Long-term effects of early kwashiorkor compared with marasmus. II. Intellectual performance

Journal of pediatric …, 1987

Physical growth and sexual maturation were measured in a follow-up study of Barbadian girls and b... more Physical growth and sexual maturation were measured in a follow-up study of Barbadian girls and boys aged 11-18 years with histories of kwashiorkor (n = 54) or marasmus (n = 56) in their first year of life. They were compared with healthy neighborhood children matched by sex and age who had normal patterns of growth in early childhood (n = 59). Girls with histories of marasmus had significant delays in the onset of menarche compared with healthy comparison girls. However, their rate of growth during the previous 2 years was accelerated, and the differences in size were smaller than at the earlier testing, confirming catch-up. This pattern was not evident for girls with histories of kwashiorkor, who did not differ from the healthy comparison girls on either onset of menarche, Tanner ratings of sexual maturation, or measures of physical growth. In contrast, boys with histories of kwashiorkor or marasmus did not differ from healthy comparison boys in physical growth or Tanner ratings at these ages.

Research paper thumbnail of A preliminary study of temperament among malnourished Mayan children

Nutritional Neuroscience 1:141-149, 1998

Research paper thumbnail of Prenatally malnourished female but not male rats show increased sensitivity to MK-801 in a differential reinforcement of low rates task

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and c... more A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-depend...

Research paper thumbnail of The neural basis of attentional alterations in prenatally protein malnourished rats

Protein malnutrition during gestation alters brain development and produces specific behavioral a... more Protein malnutrition during gestation alters brain development and produces specific behavioral and cognitive changes that persist into adulthood and increase the risks of neuropsychiatric disorders. Given evidence for the role of the prefrontal cortex in such diseases, it is significant that studies in humans and animal models have shown that prenatal protein malnutrition specifically affects functions associated with prefrontal cortex. However, the neural basis underlying these changes is unclear. In the current study, prenatally malnourished and control rats performed a sustained attention task with an unpredictable distractor, a task that depends on intact prefrontal cortical function. Radiolabeled 2-deoxyglucose was used to measure neural and brain network activity during the task. Results confirmed that adult prenatally malnourished rats were more distractible than controls and exhibited lower functional activity in prefrontal cortices. Thus, prefrontal activity was a predicto...

Research paper thumbnail of Effect of Prenatal Protein Malnutrition on Birthdates and Number of Neurons in the Rat Locus Coeruleus

The effect of prenatal protein deprivation on the timing of neurogenesis and on the number of neu... more The effect of prenatal protein deprivation on the timing of neurogenesis and on the number of neurons generated in the locus coeruleus of the rat was studied. These neurons are of interest as their axon projections are involved in the earliest stages of cerebral cortical development. Dams were maintained on a 25% casein diet or a 6% casein diet five weeks prior to mating and the diets continued throughout the pregnancy. At birth, all pups were cross-fostered to dams on a 25% casein diet. BrDU, a thymidine analog that is incorporated into the nuclear DNA during the synthetic phase of the cell cycle, was used as a marker of the generation period. It was administered intraperitoneally (25 mg/kg body weight) on embryonic day 10, 11, 12, 13, or 14. On postnatal day 30, the brain stems were processed with BrDU immunocytochemistry to determine the relative number of neurons generated on each day, and with Nissl stain to determine the total number of neurons generated in the two groups. The...

Research paper thumbnail of The neural basis of attentional alterations in prenatally protein malnourished rats

Cerebral Cortex

Protein malnutrition during gestation alters brain development and produces specific behavioral a... more Protein malnutrition during gestation alters brain development and produces specific behavioral and cognitive changes that persist into adulthood and increase the risks of neuropsychiatric disorders. Given evidence for the role of the prefrontal cortex in such diseases, it is significant that studies in humans and animal models have shown that prenatal protein malnutrition specifically affects functions associated with prefrontal cortex. However, the neural basis underlying these changes is unclear. In the current study, prenatally malnourished and control rats performed a sustained attention task with an unpredictable distractor, a task that depends on intact prefrontal cortical function. Radiolabeled 2-deoxyglucose was used to measure neural and brain network activity during the task. Results confirmed that adult prenatally malnourished rats were more distractible than controls and exhibited lower functional activity in prefrontal cortices. Thus, prefrontal activity was a predicto...

Research paper thumbnail of Impact of early childhood malnutrition on the adult brain function: an ERP study

According to the World Health Organization, 45% of deaths among children under 5 years of age are... more According to the World Health Organization, 45% of deaths among children under 5 years of age are caused by childhood malnutrition, which affects 224 million children worldwide. The Barbados Nutrition Study (BNS) is a 50+year longitudinal study on a Barbadian cohort (N=258) with histories of moderate to severe protein-energy malnutrition (PEM) in the first year of life and healthy controls. Interestingly, a recent BNS publication used quantitative electroencephalography (EEG) to show differences in brain function (lower alpha1 activity and higher theta, alpha2 and beta activity) in children who suffered from early PEM compared to healthy controls. However, the adult brain function following early childhood PEM has not been reported in this cohort. In the current study, EEG recordings were undertaken during a Go-No-Go task on a subsample of the BNS cohort (n=55) at ages 45-51 years. Evoked-related potentials (ERP) analyses show that, compared to the control group (n=29), participants...

Research paper thumbnail of Prenatal protein level impacts homing behavior in Long-Evans rat pups

Nutritional neuroscience, Jan 20, 2015

Objective This study assessed the effect of varying prenatal protein levels on the development of... more Objective This study assessed the effect of varying prenatal protein levels on the development of homing orientation in rat pups. Methods Long-Evans rats were fed one of the four isocaloric diets containing 6% (n = 7 litters), 12% (n = 9), 18% (n = 9), or 25% (n = 10) casein prior to mating and throughout pregnancy. At birth, litters were fostered to well-nourished control mothers fed a 25% casein diet during pregnancy, and an adequate protein diet (25% casein) was provided to weaning. On postnatal days 5, 7, 9, 11, and 13, homing behaviors, including activity levels, rate of successful returns to the nest quadrant and latencies to reach the nest over a 3-minute test period were recorded from two starting positions in the home cage. Adult body and brain weights were obtained at sacrifice (postnatal day 130 or 200). Results Growth was impaired in pups whose mothers were fed a 6% or, to a lesser extent, a 12% casein diet relative to pups whose mothers were fed the 18 and 25% casein di...

Research paper thumbnail of Prenatal protein malnutrition decreases KCNJ3 and 2DG activity in rat prefrontal cortex

Neuroscience, Jan 12, 2015

Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior includi... more Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in the PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with (14)C-2-deoxyglucose. Results showed decreased activation in the PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity.

Research paper thumbnail of Development and modulation of GABA(A) receptor-mediated neurotransmission in the CA1 region of prenatally protein malnourished rats

Nutritional neuroscience, 2001

Prenatal protein malnutrition has been demonstrated to result in alterations in the serotonergic ... more Prenatal protein malnutrition has been demonstrated to result in alterations in the serotonergic and GABAergic neurotransmitter systems in the rat hippocampus. In the present study, whole-cell patch clamp recordings of CA1 pyramidal cells were employed in an effort to gain insight into the specific cellular locus and functional consequences of the previously reported changes. Hippocampal slices were prepared from Sprague-Dawley rats whose dams were fed either a normal (25% casein) or low (6% casein) protein diet during pregnancy. The development of GABA(A) receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) and their modulation by the benzodiazipine agonist zolpidem were compared in cells from the two nutritional groups at postnatal days 7, 14, 21 and >90. The modulation of mIPSCs by serotonin was also examined in cells from 21 day old rats. No significant differences were observed in the characteristics of mIPSCs in cells from control vs. prenatally protein mal...

Research paper thumbnail of Prenatally malnourished female but not male rats show increased sensitivity to MK-801 in a differential reinforcement of low rates task

Behavioural pharmacology, 1998

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and c... more A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-depend...