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Biomedical subjects

Brian J Prendergast

Publications and source records attributed to Brian J Prendergast.

7 recordsLinked to original sources
PubMed2003

Photoperiod controls the induction, retention, and retrieval of antigen-specific immunological memory.

Changes in day length affect several measures of immunity in seasonally breeding mammals. In Siberian hamsters (Phodopus sungorus), short day lengths suppress specific secondary antibody responses to the keyhole limpet hemocyanin (KLH) antigen and enhance cutaneous delayed-type hypersensitivity (DTH) responses to dinitrofluorobenzene (DNFB). These experiments tested whether day length affects secondary antibody and DTH responses by altering immune function solely during the interval after the initial exposure to each antigen, solely during the interval after the second exposure, or during both stages of the respective immune responses. Adult male Siberian hamsters were exposed to either a long (16 h light/day; LD) or a short (8 h light/day; SD) photoperiod for 7.5 wk before receiving an initial exposure to each antigen (KLH injection, cutaneous DNFB treatment; separate groups of animals for each antigen). A subset of LD hamsters was transferred to the SD photo-period, and a subset of SD hamsters was transferred to the LD photoperiod. Other hamsters remained in LD or SD. Eight weeks later, all hamsters were challenged with a second subcutaneous injection of KLH or a second application of DNFB to the ear, and immune responses were measured. Exposure to SD during the primary antibody response did not affect secondary IgG responses, but SD exposure during the secondary response significantly suppressed IgG production independent of day length during the initial KLH treatment. In contrast, exposure to SD during the DNFB challenge enhanced the ensuing DTH response, but this enhancement depended on the photoperiod prevailing during the initial exposure. Exposure to SD during the sensitization stage did not enhance DTH in hamsters subsequently exposed to LD. The data suggest that short photoperiods have enduring effects on immune responsiveness and on the establishment and retention of immunological memory.

Animals↗
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

Temporal integration of melatonin infusion duration: signal averaging versus frequency dependence.

Day length affects somatic and reproductive physiology of Siberian hamsters via regulation of the duration of nocturnal pineal melatonin secretion. Nightly 'long' (e.g. 12 hr) or 'short' (e.g. 6 hr) melatonin signals inhibit or stimulate gonadal growth, respectively. When long and short signals are presented in combination, however, neuroendocrine mechanisms exhibit a frequency-dependent response, stimulating gonadal growth only if short signals are presented every second night or more frequently. The present experiments further assessed formal models for the temporal integration of melatonin signals changing abruptly in duration from night to night. Photo-inhibited Siberian hamsters were housed in constant light and infused subcutaneously with various combinations of nightly short or long melatonin signals according to one of the several regimes that varied the frequency of short melatonin signal occurrence, average duration of the nightly melatonin signal, or both. Six weeks of nightly alternating short and long signals yielded different gonadal responses depending on the average melatonin signal duration. Moreover, when average melatonin signal duration was held constant between groups, gonadal stimulation was independent of the frequency of the constituent melatonin signals except when the duration of the short signal was reduced to 3 hr. Thus, neuroendocrine mechanisms do not solely categorize melatonin signals as either long or short but attend also to the duration of each component signal. In the majority (six of seven) of infusion regimes, reproductive responses to chimeric patterns of long and short melatonin signals were compatible with a simple signal-averaging mechanism.

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

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.

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