Cognitive Science Program

Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase (1995)
Randy J Nelson, Gregory E Demas, Paul L Huang, Mark C Fishman, Valina L Dawson, Ted M Dawson ...
Nature, 378 (6555), 383

Abstract

IN addition to its role in blood vessel 1, 2 and macrophage 3, 4 function, nitric oxide (NO) is a neurotransmitter 5 found in high densities in emotion-regulating brain regions 6–8. Mke with targeted disruption of neuronal NO synthase (nNOS) display grossly normal appearance, locomotor activity, breeding 9, long-term potentiation 10 and long-term depression 11. The nNOS− mice are resistant to neural stroke damage following middle cerebral artery ligation 12. Although CO 2-induced cerebral vasodilatation in wild-type mice is NO− dependent, in nNOS" mice this vasodilation is unaffected by NOS inhibitors 13. Establishing a behavioural role for NO has, until now, not been feasible, as NOS inhibitor drugs can only be administered acutely and because their pronounced effects on blood pressure and other body functions obfuscate behavioural interpretations. We now report a large increase in aggressive behaviour …

Seasonal changes in immune function (1996)
Randy J Nelson and Gregory E Demas
The Quarterly review of biology, 71 (4), 511-548

Abstract

Winter is energetically demanding. Physiological and behavior adaptations have evolved among nontropical animals to cope with winter because thermoregulatory demands increase when food availability decreases. Seasonal breeding is central within the suite of winter adaptations among small animals. Presumably, reproductive inhibition during winter conserves energy at a time when the odds of producing viable young are low. In addition to the well-studied seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many populations of mammals and birds in the field. Challenging winter conditions, such as low ambient temperatures and decreased food availability, can directly induce death via hypothermia, starvation, or shock. In some cases, survival in demanding winter conditions puts individuals under great physiological stress, defined here as an adaptive …

Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice (1997)
Gregory E Demas, Vladimir Chefer, Mark I Talan and Randy J Nelson
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 273 (5), R1631-R1637

Abstract

Animals must balance their energy budget despite seasonal changes in both energy availability and physiological expenditures. Immunity, in addition to growth, thermoregulation, and cellular maintenance, requires substantial energy to maintain function, although few studies have directly tested the energetic cost of immunity. The present study assessed the metabolic costs of an antibody response. Adult and aged male C5BL/6J mice were implanted with either empty Silastic capsules or capsules filled with melatonin and injected with either saline or keyhole limpet hemocyanin (KLH). O₂ consumption was monitored periodically throughout antibody production using indirect calorimetry. KLH-injected mice mounted significant immunoglobulin G (IgG) responses and consumed more O₂ compared with animals injected with saline. Melatonin treatment increased O₂ consumption in mice injected with saline but …

Seasonal patterns of stress, immune function, and disease (2002)
Randy J Nelson, Gregory E Demas, Sabra L Klein and Lance J Kriegsfeld
Cambridge University Press.

Abstract

This book presents evidence that infection is cyclical with the seasons, and that this phenomenon is mirrored in cycles of immune function. The book identifies the mechanisms by which immune systems are bolstered to counteract seasonally-recurrent stressors, such as extreme temperature reductions and food shortages. Stress, infectious diseases, autoimmune diseases, and human cancers are examined, and the role of hormones such as melatonin and glucocorticoids is considered. The book begins with an overview of seasonality, biological rhythms and photoperiodism, and basic immunology, and then discusses seasonal fluctuations in disease prevalence, immune function, and energetics and endocrinology as they relate to immune function. The clinical significance of this issue is also addressed, as such seasonal changes may play an important role in the development and treatment of infections. This first monograph to examine seasonal immune function from an interdisciplinary perspective will serve practitioners as well as advanced undergraduates and graduate students in biology, immunology, human and veterinary medicine, neuroscience, endocrinology, and zoology.

Seasonal changes in adiposity: the roles of the photoperiod, melatonin and other hormones, and sympathetic nervous system (2002)
Timothy J Bartness, Gregory E Demas and C Kay Song
Experimental Biology and Medicine, 227 (6), 363-376

Abstract

It appears advantageous for many non-human animals to store energy body fat extensively and efficiently because their food supply is more labile and less abundant than in their human counterparts. The level of adiposity in many of these species often shows predictable increases and decreases with changes in the season. These cyclic changes in seasonal adiposity in some species are triggered by changes in the photoperiod that are faithfully transduced into a biochemical signal through the nightly secretion of melatonin (MEL) via the pineal gland. Here, we focus primarily on the findings from the most commonly studied species showing seasonal changes in adiposity—Siberian and Syrian hamsters. The data to date are not compelling for a direct effect of MEL on white adipose tissue (WAT) and brown adipose tissue (BAT) despite some recent data to the contrary. Thus far, none of the possible hormonal …

The energetics of immunity: a neuroendocrine link between energy balance and immune function (2004)
Gregory E Demas
Hormones and Behavior, 45 (3), 173-180

Abstract

Among the many significant contributions Frank A. Beach made to the field of behavioral endocrinology, particularly influential was his emphasis on the importance of integration in scientific pursuits; Beach believed that to fully understand physiology and behavior, one needed to understand not only the interrelationships among behavior and the nervous and endocrine systems, but also the complex dynamics that occur within the ecological context of the environment in which an animal lives. Furthermore, the mechanisms of behavior must also be understood in an evolutionary framework. Thus, it was Beach’s strong belief that an ‘‘integrative psychobiology would transcend all levels of analysis’’and would be ‘‘rooted in the study of its physiological correlates on the one hand and its adaptive function on the other’’(Dewsbury, 1988). As students of behavioral neuroendocrinology, application of an integrative approach to the study of hormones, brain, and behavior remains one of our greatest challenges. This review will focus on how an integrative approach to the study of neuroendocrine–immune interactions can be useful in addressing important questions regarding the neural and hormonal mechanisms underlying the energetic regulation of immunity.

Beyond phytohaemagglutinin: assessing vertebrate immune function across ecological contexts (2011)
Gregory E Demas, Devin A Zysling, Brianna R Beechler, Michael P Muehlenbein and Susannah S French
Journal of Animal Ecology, 80 (4), 710-730

Abstract

1. Over the past decade, there has been a substantial increase in interest in the immune system and the role it plays in the regulation of disease susceptibility, giving rise to the field of eco‐immunology. 2. Eco‐immunology aims to understand changes in host immune responses in the broader framework of an organism’s evolutionary, ecological and life‐history contexts. 3. The immune system, however, is complex and multifaceted and can be intimidating for the nonimmunologist interested in incorporating immunological questions into their research. Which immune responses should one measure and what is the biological significance of these measures? 4. The focus of this review is to describe a wide range of eco‐immunology techniques, from the simple to the sophisticated, with the goal of providing researchers with a range of options to consider incorporating in their own research programs. 5. These …

Environmental control of kisspeptin: implications for seasonal reproduction (2007)
Timothy J Greives, Alex O Mason, Melissa-Ann L Scotti, Jacob Levine, Ellen D Ketterson, Lance J Kriegsfeld ...
Endocrinology, 148 (3), 1158-1166

Abstract

The KiSS-1 gene encodes the peptide hormone kisspeptin, which acts as a principal positive regulator of the reproductive axis by directly stimulating GnRH neuron activity. To gain insight into a potential role for kisspeptin in integrating and relaying reproductively relevant stimuli to the GnRH system, we investigated changes in kisspeptin peptide expression associated with photoperiodic changes in reproductive state as well as pituitary and gonadal responses to peripheral kisspeptin injections. Seasonally breeding rodents undergo pronounced fluctuations in reproductive state in response to changing day lengths. In common with other rodent species, a majority of male Siberian hamsters (Phodopus sungorus) exhibit reproductive decline after exposure to short-day lengths. A subset of individuals fails to respond to day length information, however, and maintains their reproductive function. We exploited these …

SCN efferents to peripheral tissues: implications for biological rhythms (2001)
TJ Bartness, CK Song and GE Demas
Journal of biological rhythms, 16 (3), 196-204

Abstract

The suprachiasmatic nucleus (SCN) is the principal generator of circadian rhythms and is part of an entrainment system that synchronizes the animal with its environment. Here, the authors review the possible communication of timing information from the SCN to peripheral tissues involved in regulating fundamental physiological functions as revealed using a viral, transneuronal tract tracer, the pseudorabies virus (PRV). The sympathetic nervous system innervation of the pineal gland and the sympathetic outflow from brain to white adipose tissue were the first demonstrations of SCN-peripheral tissue connections. The inclusion of the SCN as part of these and other circuits was the result of lengthened postviral injection times compared with those used previously. Subsequently, the SCN has been found to be part of the sympathetic outflow from the brain to brown adipose tissue, thyroid gland, kidney, bladder, spleen …

Novel mechanisms for neuroendocrine regulation of aggression (2008)
Kiran K Soma, Melissa-Ann L Scotti, Amy EM Newman, Thierry D Charlier and Gregory E Demas
Academic Press. 29 (4), 476-489

Abstract

In 1849, Berthold demonstrated that testicular secretions are necessary for aggressive behavior in roosters. Since then, research on the neuroendocrinology of aggression has been dominated by the paradigm that the brain receives gonadal hormones, primarily testosterone, which modulate relevant neural circuits. While this paradigm has been extremely useful, recent studies reveal important alternatives. For example, most vertebrate species are seasonal breeders, and many species show aggression outside of the breeding season, when gonads are regressed and circulating testosterone levels are typically low. Studies in birds and mammals suggest that an adrenal androgen precursor—dehydroepiandrosterone (DHEA)—may be important for the expression of aggression when gonadal testosterone synthesis is low. Circulating DHEA can be metabolized into active sex steroids within the brain. Another …

Stroke in estrogen receptor--deficient mice (2000)
Kenji Sampei, Shozo Goto, Nabil J Alkayed, Barbara J Crain, Kenneth S Korach, Richard J Traystman ...
Stroke, 31 (3), 738-744

Abstract

Background and Purpose—Recent evidence suggests that endogenous estrogens or hormone replacement therapy can ameliorate brain damage from experimental stroke. Protective mechanisms involve enhanced cerebral vasodilation during ischemic stress as well as direct preservation of neuronal viability. We hypothesized that if the intracellular estrogen receptor subtype-α (ERα) is important to estrogen’s signaling in the ischemic brain, then ERα-deficient (knockout)(ERαKO) female mice would sustain exaggerated cerebral infarction damage after middle cerebral artery occlusion.Methods—The histopathology of cresyl violet–stained tissues was evaluated after reversible middle cerebral artery occlusion (2 hours, followed by 22 hours of reperfusion) in ERαKO transgenic and wild-type (WT) mice (C57BL/6J background strain). End-ischemic cerebral blood flow mapping was obtained from additional female murine cohorts by using [14C] iodoantipyrine autoradiography.Results—Total hemispheric tissue damage was not altered by ERα deficiency in female mice: 51.910. 6 mm3 in ERαKO versus 60.55. 0 mm3 in WT. Striatal infarction was equivalent, 12.21. 7 mm3 in ERαKO and 13.41. 0 mm3 in WT mice, but cortical infarction was paradoxically smaller relative to that of the WT (20.74. 5 mm3 in ERαKO versus 30.64. 1 mm3 in WT). Intraocclusion blood flow to the parietal cortex was higher in ERαKO than in WT mice, likely accounting for the reduced infarction in this anatomic area. There were no differences in stroke outcomes by region or genotype in male animals.Conclusions—Loss of ERα does not enhance tissue damage in the female …

Minireview The influence of season, photoperiod, and pineal melatonin on immune function (1995)
Randy J Nelson, Gregory E Demas, Sabra L Klein and Lance J Kriegsfeld
Journal of pineal research, 19 (4), 149-165

Abstract

In addition to the well‐documented seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many animal populations. Challenging winter conditions (i.e., low ambient temperature and decreased food availability) can directly induce death via hypothermia, starvation, or shock. Coping with these challenges can also indirectly increase morbidity and mortality by increasing glucocorticoid secretion, which can compromise immune function. Many environmental challenges are recurrent and thus predictable; animals could enhance survival, and presumably increase fitness, if they could anticipate immunologically challenging conditions in order to cope with these seasonal threats to health. The annual cycle of changing photoperiod provides an accurate indicator of time of year and thus allows immunological adjustments prior to the deterioration of conditions. Pineal …

Spatial memory deficits in segmental trisomic Ts65Dn mice (1996)
Gregory E Demas, Randy J Nelson, Bruce K Krueger and Paul J Yarowsky
Behavioural brain research, 82 (1), 85-92

Abstract

Spatial memory was assessed in the segmental trisomic 16 mouse (Ts65Dn), a potential model for Down syndrome (DS), using the 12-arm radial maze (RAM). Ts65Dn mice have a portion of mouse chromosome 16 syntenic to the distal end of human chromosome 21 triplicated. On each of 8 daily trials of the RAM, Ts65Dn mice made fewer correct choices than control mice and performed at or near chance levels, indicating a deficit in spatial working memory. On trials 9 and 10, Ts65Dn mice performed as well as control mice on the initial 12 choices, but required a greater number of choices to complete the RAM. The improved performance of Ts65Dn mice on trials 9 and 10 was lost when the animals were retested after a 50-day retention period, suggesting that long-term memory is also defective. These results are not likely explained by differences in either response bias or perceptual discrimination. Ts65Dn and …

Ecoimmunology (2012)
Gregory Demas and Randy Nelson
Oxford University Press.

Abstract

The role of parasites and pathogens in the evolution of life history traits is of increasing interest to both ecologists and evolutionary biologists. Immunology, which was once studied almost exclusively by immunologists, has become an important area of proximate investigation to animal physiologists as a means for understanding changes in disease susceptibility and the neural and neuroendocrine mechanisms that mediate these changes. The coalescence of these different perspectives has given rise to the field of ecological immunology, an interdisciplinary research field that examines interactions among host physiology and disease ecology in a wide range of environmentally relevant contexts. The goal of ecological immunology is to understand immune function in the context of life-history traits across a wide range of organisms. Research within the field combines diverse approaches from a wide range of scientific disciplines including evolution, ecology, and life history theory to endocrinology, neuroscience, molecular biology, and behavior. This book critically reviews recent advances in the discipline of ecoimmunology. Chapters are written by experts in their respective fields and cover diverse topics including how environmental factors can affect host immune function, the complex dynamics among host immunity, pathogen prevalence and disease susceptibility, and the physiological mechanisms that lead to adaptive changes in immune responses. By integrating analyses of immune system function within animal biology, investigators will gain will gain a more comprehensive and satisfying understanding of organism-environment interactions …

Short-day increases in aggression are inversely related to circulating testosterone concentrations in male Siberian hamsters (Phodopus sungorus) (2000)
Aaron M Jasnow, Kim L Huhman, Timothy J Bartness and Gregory E Demas
Hormones and behavior, 38 (2), 102-110

Abstract

Many nontropical rodent species display seasonal changes in both physiology and behavior that occur primarily in response to changes in photoperiod. Short-day reductions in reproduction are due, in part, to reductions in gonadal steroid hormones. In addition, gonadal steroids, primarily testosterone (T), have been implicated in aggression in many mammalian species. Some species, however, display increased aggression in short days despite basal circulating concentrations of T. The goal of the present studies was to test the effects of photoperiod on aggression in male Siberian hamsters (Phodopus sungorus) and to determine the role of T in mediating photoperiodic changes in aggression. In Experiment 1, hamsters were housed in long and short days for either 10 or 20 weeks and aggression was determined using a resident-intruder model. Hamsters housed in short days for 10 weeks underwent gonadal …