PubMed Health⌕ Search

Biomedical subjects

Randy J Nelson

Publications and source records attributed to Randy J Nelson.

13 recordsLinked to original sources
PubMed2003

Reductions in total body fat decrease humoral immunity.

Mounting an immune response requires substantial energy, and it is well known that marked reductions in energy availability (e.g. starvation) can suppress immune function, thus increasing disease susceptibility and compromising survival. We tested the hypothesis that moderate reductions in energy availability impair humoral immunity. Specifically, we examined the effects of partial lipectomy (LIPx) on humoral immunity in two seasonally breeding rodent species, prairie voles (Microtus ochrogaster) and Siberian hamsters (Phodopus sungorus). Animals received bilateral surgical removal of epididymal white adipose tissue (EWATx), inguinal white adipose tissue (IWATx) or sham surgeries and were injected with the antigen keyhole limpet haemocyanin (KLH) either four or 12 weeks after surgery. In prairie voles, serum anti-KLH immunoglobulin G (IgG) did not differ significantly at four weeks. At 12 weeks, serum IgG was significantly reduced in IWATx, but not EWATx animals, compared with sham-operated animals. In Siberian hamsters, both IWATx and EWATx animals reduced serum IgG at four weeks. At 12 weeks, EWATx hamsters displayed a significant compensatory increase in IWAT pad mass compared with sham-operated hamsters, and serum IgG no longer differed from sham-operated animals. There was no significant increase in EWAT in IWATx hamsters compared with sham animals and IgG remained significantly reduced in IWATx hamsters. These results suggest that reductions in energy availability can impair humoral immunity.

Adipose Tissue↗
PubMed2003

Photoperiod and stress affect wound healing in Siberian hamsters.

Changes in day length alter several indices of immune function in Siberian hamsters. These experiments tested the hypothesis that photoperiodic changes in immune function are integrated at an organismal level as reflected by the ability to heal a cutaneous wound. Given the well-documented effects of psychological stressors on immune function, we also tested the hypothesis that photoperiod modulates the effects of acute stress on wound healing. Male hamsters were housed in long (16L:8D; LD) or short (8L:16D; SD) day lengths for 8+/-2 weeks. SD-treatment was sufficient to induce winter reproductive status. Hamsters then received a dermal punch wound. Hamsters were subjected to either 2 h of daily restraint stress or a control treatment for 3 days prior to and 5 days after wounding. Wounds were digitally photographed daily, and wound size was measured to quantify healing. Wounds of LD hamsters healed significantly faster than did those of SD hamsters. Restraint stress significantly accelerated healing in SD hamsters. The results suggest that the enhancing effects of short-term psychological stressors on immune function are apparent only when reproductive function is suppressed. In nature, enhanced wound healing coincident with the breeding season and territorial defense may be adaptive.

Animals↗
PubMed2003

Photoperiodic adjustments in immune function protect Siberian hamsters from lethal endotoxemia.

Seasonal changes in day length enhance or suppress components of immune function in individuals of several mammalian species. Siberian hamsters (Phodopus sungorus) exhibit multiple changes in neuroendocrine, reproductive, and immune function after exposure to short days. The manner in which these changes are integrated into the host response to pathogens is not well understood. The present experiments tested the hypothesis that short-day changes in immune function alter the pathogenesis of septic shock and survival after challenge with endotoxin. Male and female Siberian hamsters raised in long-day photoperiods were transferred as adults to short days or remained in their natal photoperiod. Six to 8 weeks later, hamsters were injected i.p. with 0, 1, 2.5, 10, 25, or 50 mg/kg bacterial lipopolysaccharide (LPS) (the biologically active constituent of endotoxin), and survival was monitored for 96 h. Short days significantly improved survival of male hamsters treated with 10 or 25 mg/kg LPS and improved survival in females treated with 50 mg/kg LPS. Transfer from long to short days shifted the LD50 in males by approximately 90%, from 5.3 to 9.9 mg/kg, and in females from 11.1 to 15.0 mg/kg (+35%). Long-day females were more resistant than were males to lethal endotoxemia. In vitro production of the proinflammatory cytokine TNFalpha in response to LPS stimulation was significantly lower in macrophages extracted from short-day relative to long-day hamsters, as were circulating concentrations of TNFalpha in vivo after i.p. administration of LPS, suggesting that diminished cytokine responses to LPS in short days may mitigate the lethality of endotoxemia. Adaptation to short days induces changes in immune parameters that affect survival in the face of immune challenges.

Animals↗
PubMed2002

Hypothalamic gene expression in reproductively photoresponsive and photorefractory Siberian hamsters.

An interval timing mechanism in the brain governs reproduction in seasonally breeding mammals by triggering refractoriness to inhibitory short photoperiods during midwinter. The neural mechanisms responsible for the timing and induction of photorefractoriness by this seasonal clock are unknown. Using cDNA microarrays and RT-PCR, we identified a class of genes encoding thyroxine (T4)-binding proteins (transthyretin, T4-binding globulin, albumin) whose expression is associated with reproductive refractoriness to short day lengths. Down-regulation of these genes was associated with reduced hypothalamic T4 uptake, which was reversed by long-day photoperiod treatments that restored responsiveness to short days. Circulating T4 concentrations did not vary with states of photoresponsiveness in euthyroid hamsters, but blockade of thyroid function accelerated the onset of photorefractoriness to short days. These data link changes in gene expression in the hypothalamus to the functional output of a seasonal clock. Reproductive inhibition in short days depends on T4 only late in the nonbreeding season. Down-regulation of genes encoding T4-binding proteins in the hypothalamus during this interval may restrict access of a static T4 signal to hypothalamic target tissues that regulate reproduction, thereby timing annual transitions in reproductive function. Hypothalamic autoregulation of T4 influx may constitute a critical cellular process involved in the generation and expression of seasonal reproductive rhythms and suggests a previously undescribed mechanism by which neural targets gain access to peripheral hormones.

Albumins↗
PubMed2002

A role for the melanocortin 4 receptor in sexual function.

By using a combination of genetic, pharmacological, and anatomical approaches, we show that the melanocortin 4 receptor (MC4R), implicated in the control of food intake and energy expenditure, also modulates erectile function and sexual behavior. Evidence supporting this notion is based on several findings: (i) a highly selective non-peptide MC4R agonist augments erectile activity initiated by electrical stimulation of the cavernous nerve in wild-type but not Mc4r-null mice; (ii) copulatory behavior is enhanced by administration of a selective MC4R agonist and is diminished in mice lacking Mc4r; (iii) reverse transcription (RT)-PCR and non-PCR based methods demonstrate MC4R expression in rat and human penis, and rat spinal cord, hypothalamus, brainstem, pelvic ganglion (major autonomic relay center to the penis), but not in rat primary corpus smooth muscle cavernosum cells; and (iv) in situ hybridization of glans tissue from the human and rat penis reveal MC4R expression in nerve fibers and mechanoreceptors in the glans of the penis. Collectively, these data implicate the MC4R in the modulation of penile erectile function and provide evidence that MC4R-mediated proerectile responses may be activated through neuronal circuitry in spinal cord erectile centers and somatosensory afferent nerve terminals of the penis. Our results provide a basis for the existence of MC4R-controlled neuronal pathways that control sexual function.

Animals↗
PubMed2002

Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent.

A new spontaneous mouse mutation named fierce (frc) is deleted for the nuclear receptor Nr2e1 gene (also known as Tlx, mouse homolog of Drosophila tailless). The fierce mutation is genetically and phenotypically similar to Nr2e1 targeted mutations previously studied on segregating genetic backgrounds. However, we have characterized the fierce brain, eye, and behavioural phenotypes on three defined genetic backgrounds (C57BL/6J, 129P3/JEms, and B6129F1). The data revealed many novel and background-dependent phenotypic characteristics. Whereas abnormalities in brain development, hypoplasia of cerebrum and olfactory lobes, were consistent on all three backgrounds, our novel finding of enlarged ventricles in 100% and overt hydrocephalus in up to 30% of fierce mice were unique to the C57BL/6J background. Developmental eye abnormalities were also background-dependent with B6129F1-frc mice having less severe thinning of optic layers and less affected electroretinogram responses. Impaired regression of hyaloid vessels was observed in all backgrounds. Furthermore, retinal vessels were deficient in size and number in 129P3/JEms-frc and B6129F1-frc mice but almost entirely absent in C57BL/6J-frc mice. We present the first standardized behavioural tests conducted on Nr2e1 mutant mice and show that C57BL/6J-frc and B6129F1-frc mice have deficits in sensorimotor assays and are hyperaggressive in both sexes and backgrounds. However, C57BL/6J-frc mice were significantly more aggressive than B6129F1-frc mice. Overall, this extensive characterization of the fierce mutation is essential to its application for the study of behavioural, and brain and eye developmental disorders. In addition, the background-dependent differences revealed will enable the identification of important genetic modifiers.

Aggression↗
PubMed2002

Short day lengths augment stress-induced leukocyte trafficking and stress-induced enhancement of skin immune function.

Environmental conditions influence the onset and severity of infection and disease. Stressful conditions during winter may weaken immune function and further compromise survival by means of hypothermia, starvation, or shock. To test the hypothesis that animals may use photoperiod to anticipate the onset of seasonal stressors and adjust immune function, we evaluated glucocorticoids and the distribution of blood leukocytes in Siberian hamsters (Phodopus sungorus) exposed to long day lengths (i.e., summer) or short day (SD) lengths (i.e., winter) at baseline and during acute stress. We also investigated the influence of photoperiod and acute stress on a delayed-type hypersensitivity response in the skin. SDs increased glucocorticoid concentrations and the absolute number of circulating blood leukocytes, lymphocytes, T cells, and natural killer cells at baseline in hamsters. During stressful challenges, it appears beneficial for immune cells to exit the blood and move to primary immune defense areas such as the skin, in preparation for potential injury or infection. Acute (2 h) restraint stress induced trafficking of lymphocytes and monocytes out of the blood. This trafficking occurred more rapidly in SDs compared to long days. Baseline delayed-type hypersensitivity responses were enhanced during SDs; this effect was augmented by acute stress and likely reflected more rapid redistribution of leukocytes out of the blood and into the skin. These results suggest that photoperiod may provide a useful cue by which stressors in the environment may be anticipated to adjust the repertoire of available immune cells and increase survival likelihood.

Adaptation, Physiological↗
PubMed2002

Short day lengths attenuate the symptoms of infection in Siberian hamsters.

Symptoms of infection, such as fever, anorexia and lethargy, are ubiquitous among vertebrates. Rather than nonspecific manifestations of illness, these responses are organized, adaptive strategies that are often critical to host survival. During times of energetic shortage such as winter, however, it may be detrimental for individuals to prolong energetically demanding symptoms such as fever. Individuals may adjust their immune responses prior to winter by using day length to anticipate energetically-demanding conditions. If the expression of sickness behaviours is constrained by energy availability, then cytokine production, fever, and anorexia should be attenuated in infected Siberian hamsters housed under simulated winter photoperiods. We housed hamsters in either long (14 L : 10 D) or short (10 L : 14 D) day lengths and assessed cytokines, anorexia and fever following injections of lipopolysaccharide (LPS). Short days attenuated the response to lipopolysaccharide, by decreasing the production of interleukin (IL)-6 and IL-1beta, and diminishing the duration of fever and anorexia. Short-day exposure in hamsters also decreased the ingestion of dietary iron, a nutrient vital to bacterial replication. Taken together, short day lengths attenuated the symptoms of infection, presumably to optimize energy expenditure and survival outcome.

Adaptation, Physiological↗
PubMed2002

Exposure to short days, but not short-term melatonin, enhances humoral immunity of male Syrian hamsters (Mesocricetus auratus).

Many non-tropical rodent species rely on photoperiod as the primary cue to co-ordinate seasonally appropriate changes in physiology and behavior. Among these seasonal changes, several rodent species (e.g. deer mice, prairie voles, Siberian hamsters) adjust immune function in response to changes in ambient day lengths. The goals of the present study were to examine the effects of photoperiod on immune function of Syrian hamsters (Mesocricetus auratus), and to determine the role of melatonin in mediating photoperiodic changes in immunity. In Experiment 1, male Syrian hamsters were housed in long (LD 14:10) or short days (LD 10:14) for 10 wk. In Experiment 2, hamsters were housed in long days and half of the animals were given 10 consecutive days of i.p. melatonin injections (15 microg) in the early evening, while the remaining animals received injections of the vehicle alone. After the respective experimental manipulations, animals were injected with the antigen, keyhole limpet hemocyanin (KLH), blood samples were obtained and anti-KLH IgG antibody production was assessed. In Experiment 1, short-day hamsters underwent gonadal regression and reduced serum testosterone as well as displayed increased humoral immune function compared with long-day animals. In Experiment 2, short-term melatonin treatment did not affect gonadal mass, testosterone or humoral immune function. These results confirm previous findings of photoperiodic changes in immunity in rodents and suggest that changes in humoral immunity are not due to short-term changes in melatonin.

Animals↗
PubMed2002

Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels.

Golden-mantled ground squirrels (Spermophilus lateralis) undergo seasonal hibernation during which core body temperature (T(b)) values are maintained 1-2 degrees C above ambient temperature. Hibernation is not continuous. Squirrels arouse at approximately 7-day intervals, during which T(b) increases to 37 degrees C for approximately 16 h; thereafter, they return to hibernation and sustain low T(b)s until the next arousal. Over the course of the hibernation season, arousals consume 60-80% of a squirrel's winter energy budget, but their functional significance is unknown and disputed. Host-defense mechanisms appear to be downregulated during the hibernation season and preclude normal immune responses. These experiments assessed immune function during hibernation and subsequent periodic arousals. The acute-phase response to bacterial lipopolysaccharide (LPS) was arrested during hibernation and fully restored on arousal to normothermia. LPS injection (ip) resulted in a 1-1.5 degrees C fever in normothermic animals that was sustained for > 8 h. LPS was without effect in hibernating squirrels, neither inducing fever nor provoking arousal, but a fever did develop several days later, when squirrels next aroused from hibernation; the duration of this arousal was increased sixfold above baseline values. Intracerebroventricular infusions of prostaglandin E(2) provoked arousal from hibernation and induced fever, suggesting that neural signaling pathways that mediate febrile responses are functional during hibernation. Periodic arousals may activate a dormant immune system, which can then combat pathogens that may have been introduced immediately before or during hibernation.

Animals↗
PubMed2002

Melatonin regulates energy balance and attenuates fever in Siberian hamsters.

Fever is considered an important host defense response but requires significant metabolic energy. During winter many animals must balance immune function with competing physiological demands (i.e. thermoregulation) to survive. Winterlike patterns of melatonin secretion induce a number of energy-saving adaptations. For instance, Siberian hamsters attenuate the duration of fever during simulated short winter day lengths, presumably to conserve energy. To determine the proximate role of melatonin in mediating this photoperiodic response, hamsters housed in long days were injected with saline or melatonin 4 h before lights off for either 1 or 6 wk and assessed for fever following injections of bacterial lipopolysaccharide. Fever duration was attenuated (32%) only in hamsters that decreased body mass, increased cortisol, and exhibited gonadal regression in response to 6 wk of melatonin. Because melatonin-treated hamsters lost significant body mass, fever was assessed in a second long-day group following ad libitum food intake, food restriction, or 24-h food deprivation. Food restriction sufficient to reduce body mass by approximately 25%, but not to reduce leptin, did not influence fever, and 24-h food deprivation virtually abolished fever. Our data suggest that long-term exposure to long-duration melatonin signals is required to induce the physiological changes necessary for short-day immune responses, perhaps involving interactions with hormones such as cortisol and leptin.

Animals↗
PubMed2002

Melatonin and immune function: hype or hypothesis?

Outside of the tropics, the combined challenge of food shortage and low temperature makes winter a particularly difficult time for reproduction and survival. Traditionally, vertebrate physiologists interested in seasonal phenomena have focused on reproduction and largely ignored survival. Our goal is to emphasize a new dimension to the study of seasonality by shifting the focus from reproduction to immune function and survival. Our hypothesis is that mechanisms enhancing immune function have evolved that enable individuals to anticipate predictable seasonal challenges that may adversely affect immunity. Stated differently, we visualize seasonal variations in survival as the interaction between two factors: the suppression of immune response due to changing energetic conditions and an endogenous rhythm of enhancement of immune response that is dependent on photoperiod, clocks, and melatonin. In this article, we review evidence of photoperiod influences on seasonal changes in immune function within the context of energy allocation. Further, we also examine mounting evidence that the pattern of melatonin secretion, mediated by photoperiod, directly influences immune function.

Adaptation, Physiological↗