Laura Fonken - Academia.edu (original) (raw)

Papers by Laura Fonken

Background: Prior experimental and epidemiologic data support a link between exposure to fine amb... more Background: Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM 2.5 ) and development of insulin resistance/Type II diabetes mellitus (Type II DM). We investigated the role of hypothalamic inflammation in PM 2.5 -mediated diabetes development.

In most parts of the world, environmental conditions vary in a predictable seasonal manner. Thus,... more In most parts of the world, environmental conditions vary in a predictable seasonal manner. Thus, seasonal variation in reproductive timing and immune function has emerged in some species to cope with disparate seasonal demands. During the long days of spring and summer when food availability is high and thermoregulatory demands low, Siberian hamsters invest in reproduction, whereas during the harsh short days of winter hamsters divert energy away from reproductive activities and modify immune capabilities. Many seasonal adaptations can be recapitulated in a laboratory setting by adjusting day length (photoperiod). Early-life photoperiods are important sources of seasonal information and can establish an individual's developmental trajectory. Siberian hamsters housed under short days (SD; 8 h light/ day) recover more rapidly than long-day (LD; 16 h light/day) hamsters from immune activation with lipopolysaccharide (LPS). SD hamsters attenuate fever response, reduce cytokine production, and abrogate behavioral responses following LPS injection. The mechanism by which SD Siberian hamsters attenuate febrile response remains unspecified. It is possible that periphery-to-brain communication of inflammatory signals is altered by exposure to photoperiod. Rather than testing photoperiod effects on each of the multiple routes by which immunological cues are communicated to the CNS, we administered LPS intracerebroventricularly (i.c.v.) following adolescent exposure to either 6 weeks of SD or LD. Injection of LPS i.c.v. led to a similar immune reaction in SD hamsters as previously reported with intraperitoneal injection. Short days attenuated the response to LPS with diminished fever spike and duration, as well as decreased locomotor inactivity. Furthermore, only LD hamsters demonstrated anhedonic-like behavior following LPS injection as evaluated by decreased preference for a milk solution. These results suggest that photoperiodic differences in response to infection are due in part to changes in central immune activation.

Particle and Fibre Toxicology, 2014

Physiology and Behavior, 2010

Darwinian fitness reflects trade-offs between reproduction and survival. Mechanisms have evolved ... more Darwinian fitness reflects trade-offs between reproduction and survival. Mechanisms have evolved in small nontropical mammals and birds to maximize reproductive output during the summer when thermoregulatory demands are relatively low and food is abundant and to shunt energy to processes that presumably increase the odds of survival during the winter when thermoregulatory demands are high and food is scarce. In order to predict the onset of winter, many seasonally-breeding mammals use day length (photoperiod) information. Seasonal adjustments of immune responses may be one mechanism to enhance survival; short days enhance cell-mediated immune function in seasonally-breeding rodents. The goal of the present study was to determine whether delayed-type hypersensitivity in hamsters is constrained or if photoperiod merely establishes a baseline level of immune response that can then be fined tuned by other environmental conditions. To test this, we used environmental enrichment, a manipulation that enhances many aspects of immune function. Hamsters were assigned to either long or short photoperiods and further assigned into either singly-housed or environmentally-enriched cages. After 10 weeks of concurrent photoperiod and housing treatment, delayed-type hypersensitivity (DTH) was induced. Although short days enhanced DTH responses compared with long days, environmental enrichment enhanced swelling responses in both short days and long days, suggesting that even during potential energetic bottlenecks or during maximal reproductive investment, hamsters can modulate their investment in immune function.

F1000 Medicine Reports, 2011

Technological advances, while providing many benefits, often create circumstances that differ fro... more Technological advances, while providing many benefits, often create circumstances that differ from the conditions in which we evolved. With the wide-spread adoption of electrical lighting during the 20 th century, humans became exposed to bright and unnatural light at night for the first time in their evolutionary history. Electrical lighting has led to the wide-scale practice of 24-hour shift-work and has meant that what were once just "daytime" activities now run throughout the night; in many ways Western society now functions on a 24-hour schedule. Recent research suggests that this gain in freedom to function throughout the night may also come with significant repercussions. Disruption of our naturally evolved light and dark cycles can result in a wide range of physiological and behavioral changes with potentially serious medical implications. In this article we will discuss several mechanisms through which light at night may exert its effects on cancer, mood, and obesity, as well as potential ways to ameliorate the impact of light at night.

Psychoneuroendocrinology, 2011

Physiology & Behavior, 2014

Most organisms display circadian rhythms that coordinate complex physiological and behavioral pro... more Most organisms display circadian rhythms that coordinate complex physiological and behavioral processes to optimize energy acquisition, storage, and expenditure. Disruptions to the circadian system with environmental manipulations such as nighttime light exposure alter metabolic energy homeostasis. Exercise is known to strengthen circadian rhythms and to prevent weight gain. Therefore, we hypothesized providing mice a running wheel for voluntary exercise would buffer against the effects of light at night (LAN) on weight gain. Mice were maintained in either dark (LD) or dim (dLAN) nights and provided either a running wheel or a locked wheel. Mice exposed to dim, rather than dark, nights increased weight gain. Access to a functional running wheel prevented body mass gain in mice exposed to dLAN. Voluntary exercise appeared to limit weight gain independently of rescuing changes to the circadian system caused by dLAN; increases in daytime food intake induced by dLAN were not diminished by increased voluntary exercise. Furthermore, although all of the LD mice displayed a 24h rhythm in wheel running, nearly half (4 out of 9) of the dLAN mice did not display a dominant 24h rhythm in wheel running. These results indicate that voluntary exercise can prevent weight gain induced by dLAN without rescuing circadian rhythm disruptions.

Proceedings of the National Academy of Sciences, 2010

The global increase in the prevalence of obesity and metabolic disorders coincides with the incre... more The global increase in the prevalence of obesity and metabolic disorders coincides with the increase of exposure to light at night (LAN) and shift work. Circadian regulation of energy homeostasis is controlled by an endogenous biological clock that is synchronized by light information. To promote optimal adaptive functioning, the circadian clock prepares individuals for predictable events such as food availability and sleep, and disruption of clock function causes circadian and metabolic disturbances. To determine whether a causal relationship exists between nighttime light exposure and obesity, we examined the effects of LAN on body mass in male mice. Mice housed in either bright (LL) or dim (DM) LAN have significantly increased body mass and reduced glucose tolerance compared with mice in a standard (LD) light/dark cycle, despite equivalent levels of caloric intake and total daily activity output. Furthermore, the timing of food consumption by DM and LL mice differs from that in LD mice. Nocturnal rodents typically eat substantially more food at night; however, DM mice consume 55.5% of their food during the light phase, as compared with 36.5% in LD mice. Restricting food consumption to the active phase in DM mice prevents body mass gain. These results suggest that low levels of light at night disrupt the timing of food intake and other metabolic signals, leading to excess weight gain. These data are relevant to the coincidence between increasing use of light at night and obesity in humans.

Pharmacology Biochemistry and Behavior, 2011

Challenging early life events can dramatically affect mental health and wellbeing. Childhood trau... more Challenging early life events can dramatically affect mental health and wellbeing. Childhood trauma and neglect can increase the risk for developing depressive, anxiety, and substance abuse disorders. Early maternal separation in rodents has been extensively studied and induces long-lasting alterations in affective and stress responses. However, other developmental periods (e.g., the pubertal period) comprise a critical window whereby social and environmental complexity can exert lasting changes on the brain and behavior. In this study, we tested whether early life environmental complexity impacts affective responses, aggressive behaviors, and expression of neuronal nitric oxide synthase (nNOS), the synthetic enzyme for nitric oxide, in adulthood. Mice were weaned into social+ nonsocial enrichment, social only enrichment, or standard (isolated) laboratory environments and were tested in open field, elevated plus maze, forced swim, and resident-intruder aggression tests 60 days later. Social+nonsocial enrichment reduced locomotor behavior and anxiety-like responses in the open field and reduced depressive-like responses in the forced swim test. Social housing increased open arm exploration in the elevated plus maze. Both social+nonsocial enrichment and social housing only reduced aggressive behaviors compared with isolation. Social+ nonsocial enrichment also increased body mass gain throughout the study. Finally, socially-housed mice had reduced corticosterone concentrations compared with social+ nonsocial-enriched mice. Behavioral testing reduced nNOS-positive neurons in the basolateral amygdala and the ventral lateral septum, but not in the social+ nonsocial-enriched mice, suggesting that environmental complexity may buffer the brain against some environmental perturbations.

Obesity, 2013

The increasing prevalence of obesity and related metabolic disorders coincides with increasing ex... more The increasing prevalence of obesity and related metabolic disorders coincides with increasing exposure to light at night. Previous studies report that mice exposed to dim light at night (dLAN) develop symptoms of metabolic syndrome. This study investigated whether mice returned to dark nights after dLAN exposure recover metabolic function. Male Swiss-Webster mice were assigned to either: standard light-dark (LD) conditions for 8 weeks (LD/LD), dLAN for 8 weeks (dLAN/dLAN), LD for 4 weeks followed by 4 weeks of dLAN (LD/dLAN), and dLAN for 4 weeks followed by 4 weeks of LD (dLAN/LD). After 4 weeks in their respective lighting conditions both groups initially placed in dLAN increased body mass gain compared to LD mice. Half of the dLAN mice (dLAN/LD) were then transferred to LD and vice versa (LD/dLAN). Following the transfer dLAN/dLAN and LD/dLAN mice gained more weight than LD/LD and dLAN/LD mice. At the conclusion of the study dLAN/LD mice did not differ from LD/LD mice with respect to weight gain and had lower fat pad mass compared to dLAN/dLAN mice. Compared to all other groups dLAN/dLAN mice decreased glucose tolerance as indicated by an intraperitoneal glucose tolerance test at week 7, indicating that dLAN/LD mice recovered glucose metabolism. dLAN/dLAN mice also increased MAC1 mRNA expression in peripheral fat as compared to both LD/LD and dLAN/LD mice, suggesting peripheral inflammation is induced by dLAN, but not sustained after return to LD. These results suggest that re-exposure to dark nights ameliorates metabolic disruption caused by dLAN exposure.

Neuroscience Letters, 2013

Melatonin is the principle hormonal product of the pineal gland. It is secreted with a robust dai... more Melatonin is the principle hormonal product of the pineal gland. It is secreted with a robust daily rhythm, peaking near the middle of the night. During the daytime, concentrations remain very low, as exposure to light robustly suppresses its secretion. The regulation of melatonin by light is well-characterized, but an interesting feature of the daily melatonin rhythm is that its peak occurs near the middle of the night and then levels begin to drop hours before morning light exposure. The mechanism underlying the light-independent drop in melatonin during late night remains unspecified. Feedback control is one mechanism of hormone regulation, but no studies thus far have explored the possibility of such regulation in the pineal of white-footed mice (Peromyscus leucopus). The pineal gland and SCN express melatonin receptors, and melatonin regulates its own receptor density in the brain. We investigated the possibility of feedback control of melatonin by administering melatonin receptor antagonists to female white-footed mice and then measuring plasma melatonin concentrations. In the first experiment, we observed that luzindole, a dual MT1/MT2 receptor antagonist administered 1h after lights off, caused an increase in plasma melatonin both 1 and 2h later. In a second experiment, we did not observe a change in melatonin concentrations following injection of an antagonist specific for the MT2 subtype. These results suggest the possibility of feedback control of melatonin release, occurring preferentially through the MT1 receptor subtype.

Molecular Psychiatry, 2011

ABSTRACT Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlyin... more ABSTRACT Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment

Molecular Psychiatry, 2011

Particulate matter air pollution is a pervasive global risk factor implicated in the genesis of p... more Particulate matter air pollution is a pervasive global risk factor implicated in the genesis of pulmonary and cardiovascular disease. Although the effects of prolonged exposure to air pollution are well characterized with respect to pulmonary and cardiovascular function, comparatively little is known about the impact of particulate matter on affective and cognitive processes. The central nervous system may be adversely affected by activation of reactive oxygen species and pro-inflammatory pathways that accompany particulate matter pollution. Thus, we investigated whether long-term exposure to ambient fine airborne particulate matter ( < 2.5 lm (PM 2.5 )) affects cognition, affective responses, hippocampal inflammatory cytokines and neuronal morphology. Male mice were exposed to either PM 2.5 or filtered air (FA) for 10 months. PM 2.5 mice displayed more depressive-like responses and impairments in spatial learning and memory as compared with mice exposed to FA. Hippocampal pro-inflammatory cytokine expression was elevated among PM 2.5 mice. Apical dendritic spine density and dendritic branching were decreased in the hippocampal CA1 and CA3 regions, respectively, of PM 2.5 mice. Taken together, these data suggest that long-term exposure to particulate air pollution levels typical of exposure in major cities around the globe can alter affective responses and impair cognition.

Journal of Pineal Research, 2011

Journal of Comparative Psychology, 2010

This study examined whether daily periods of maternal separation during the first two weeks of li... more This study examined whether daily periods of maternal separation during the first two weeks of life would decrease attraction to familiar nest odors in CD-1 mice 10 and 14 days old. We also investigated whether placing a group of mice (Mus musculus) in nest shavings during the 180-min separation period would mitigate possible separation-induced deficits. The maternal separation procedure has been widely used as a rodent model for the effects of inconsistent or inadequate early caretaking on human development. From postnatal day (PND) 1 to 14, litters were separated from the dam, but not littermates for either 15 or 180 min, or were facility-reared controls. Control, facility-reared mice preferred home-cage nest to clean familiar shaving odors on PND 10, but not PND 14. In contrast, home-cage nest odors attracted maternally separated mice on both test days. Our results suggest that maternal separation maintains the olfactory tether to the nest in a period when the attraction normally begins to weaken.

Journal of Biological Rhythms, 2012

Biological rhythms are highly adaptive, aligning individuals to daily fluctuations in the externa... more Biological rhythms are highly adaptive, aligning individuals to daily fluctuations in the external environment, as well as synchronizing internal homeostatic processes. The master mammalian circadian clock is located in the suprachiasmatic nuclei (SCN) and regulates timing of subordinate oscillators throughout the central nervous system and periphery. External lighting is important in synchronizing the circadian system and maintaining daily temporal organization. Prior to the widespread adoption of electrical lighting, individuals' biological clocks were entrained to a consistent pattern of light and dark; in contrast, modern light exists in several temporal patterns. Moreover, shift work, transmeridian travel, and inconsistent sleep schedules have rapidly increased during the past century. Because the change Abstract Circadian disruption is a common by-product of modern life. Although jet lag and shift work are well-documented challenges to circadian organization, many more subtle environmental changes cause circadian disruption. For example, frequent fluctuations in the timing of the sleep/wake schedule, as well as exposure to nighttime lighting, likely affect the circadian system. Most studies of these effects have focused on nocturnal rodents, which are very different from diurnal species with respect to their patterns of light exposure and the effects that light can have on their activity. Thus, the authors investigated the effect of nighttime light on behavior and the brain of a diurnal rodent, the Nile grass rat. Following 3 weeks of exposure to standard light/ dark (LD; 14:10 light [~150 lux] /dark [0 lux]) or dim light at night (dLAN; 14:10 light [~150 lux] /dim [5 lux]), rats underwent behavioral testing, and hippocampal neurons within CA1, CA3, and the dentate gyrus (DG) were examined. Three behavioral effects of dLAN were observed: (1) decreased preference for a sucrose solution, (2) increased latency to float in a forced swim test, and (3) impaired learning and memory in the Barnes maze. Light at night also reduced dendritic length in DG and basilar CA1 dendrites. Dendritic length in the DG positively correlated with sucrose consumption in the sucrose anhedonia task. Nighttime light exposure did not disrupt the pattern of circadian locomotor activity, and all grass rats maintained a diurnal activity pattern. Together, these data suggest that exposure to dLAN can alter affective responses and impair cognition in a diurnal animal.

Journal of Biological Rhythms, 2013

With the exception of high latitudes, life has evolved under bright days and dark nights. Most or... more With the exception of high latitudes, life has evolved under bright days and dark nights. Most organisms have developed endogenously driven circadian rhythms that are synchronized to this daily light/dark cycle. In recent years, humans have shifted away from the naturally occurring solar light cycle in favor of artificial and sometimes irregular light schedules produced by electric lighting. Exposure to unnatural light cycles is increasingly associated with obesity and metabolic syndrome; however, the means by which environmental lighting alters metabolism are poorly understood. Thus, we exposed mice to dim light at night and investigated changes in the circadian system and metabolism. Here we report that exposure to ecologically relevant levels of dim (5 lux) light at night altered core circadian clock rhythms in the hypothalamus at both the gene and protein level. Circadian rhythms in clock expression persisted during light at night; however, the amplitude of Per1 and Per2 rhythms was attenuated in the hypothalamus. Circadian oscillations were also altered in peripheral tissues critical for metabolic regulation. Exposure to dimly illuminated, as compared to dark, nights decreased the rhythmic expression in all but one of the core circadian clock genes assessed in the liver. Additionally, mice exposed to dim light at night attenuated Rev-Erb expression in the liver and adipose tissue. Changes in the circadian clock were associated with temporal alterations in feeding behavior and increased weight gain. These results are significant because they provide evidence that mild changes in environmental lighting can alter circadian and metabolic function. Detailed analysis of temporal changes induced by nighttime light exposure may provide insight into the onset and progression of obesity and metabolic syndrome, as well as other disorders involving sleep and circadian rhythm disruption.

Hormones and Behavior, 2012

Many nontropical species undergo physiological and behavioral adaptations in response to seasonal... more Many nontropical species undergo physiological and behavioral adaptations in response to seasonal changes in photoperiod, or day length. In most rodent species, short winter photoperiods reduce testosterone concentrations, which provoke gonadal regression and reduce testosterone-dependent behaviors such as mating and aggression. Seasonally-breeding Siberian hamsters, however, are paradoxically more aggressive in short-days, despite much reduced reproductive activity and testosterone concentrations. Nitric oxide (NO) signaling has been proposed as part of an alternate mechanism underlying this phenomenon. A reduction in neuronal nitric oxide synthase (nNOS), the enzyme responsible for synthesizing NO in the brain, is associated with increased aggression in male short-day hamsters. In the present study, we hypothesized that pharmacological inhibition of nNOS would increase aggressive behavior in long days, but not in short days because nNOS is already reduced. Adult male Siberian hamsters were housed in either long (LD 16:8 h) or short (LD 8:16 h) photoperiods for 8 weeks, then treated with either the selective nNOS inhibitor, 3-bromo-7-nitroindazole (3BrN) or oil vehicle, and subsequently tested for aggression in a resident-intruder test. Treatment with 3BrN increased attack frequency and duration in long days, but had no effect in short days. Short days also reduced testosterone concentrations, without any effect of treatment. These data provide further evidence linking reduced nNOS to elevated shortday aggression and support a role for NO signaling in this phenomenon.

Endocrinology, 2013

Elevated nighttime light exposure is associated with symptoms of metabolic syndrome. In industria... more Elevated nighttime light exposure is associated with symptoms of metabolic syndrome. In industrialized societies, high-fat diet (HFD) and exposure to light at night (LAN) often cooccur and may contribute to the increasing obesity epidemic. Thus, we hypothesized that dim LAN (dLAN) would provoke additional and sustained body mass gain in mice on a HFD. Male mice were housed in either a standard light/dark cycle or dLAN and fed either chow or HFD. Exposure to dLAN and HFD increase weight gain, reduce glucose tolerance, and alter insulin secretion as compared with light/dark cycle and chow, respectively. The effects of dLAN and HFD appear additive, because mice exposed to dLAN that were fed HFD display the greatest increases in body mass. Exposure to both dLAN and HFD also change the timing of food intake and increase TNF␣ and MAC1 gene expression in white adipose tissue after 4 experimental weeks. Changes in MAC1 gene expression occur more rapidly due to HFD as compared with dLAN; after 5 days of experimental conditions, mice fed HFD already increase MAC1 gene expression in white adipose tissue. HFD also elevates microglia activation in the arcuate nucleus of the hypothalamus and hypothalamic TNF␣, IL-6, and Ikbkb gene expression. Microglia activation is increased by dLAN, but only among chow-fed mice and dLAN, it does not affect inflammatory gene expression. These results suggest that dLAN exaggerates weight gain and peripheral inflammation associated with HFD.

Particle and Fibre Toxicology, 2014

Physiology and Behavior, 2010

F1000 Medicine Reports, 2011

Psychoneuroendocrinology, 2011

Physiology & Behavior, 2014

Proceedings of the National Academy of Sciences, 2010

Pharmacology Biochemistry and Behavior, 2011

Obesity, 2013

Neuroscience Letters, 2013

Molecular Psychiatry, 2011

Journal of Pineal Research, 2011

Journal of Comparative Psychology, 2010

Journal of Biological Rhythms, 2012

Journal of Biological Rhythms, 2013

Hormones and Behavior, 2012

Endocrinology, 2013