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Biomedical subjects

Deborah L Drazen

Publications and source records attributed to Deborah L Drazen.

5 recordsLinked to original sources

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↗

Photoperiod modulates the effects of norepinephrine on lymphocyte proliferation in Siberian hamsters.

Siberian hamsters (Phodopus sungorus) rely on photoperiod to coordinate seasonally appropriate changes in physiology, including immune function. Immunity is regulated, in part, by the sympathetic nervous system (SNS), although the precise role of the SNS in regulating photoperiodic changes in immunity remains unspecified. The goal of the present study was to examine the contributions of norepinephrine (NE), the predominant neurotransmitter of the SNS, to photoperiodic changes in lymphocyte proliferation. In experiment 1, animals were maintained in long [16:8-h light-dark cycle (16:8 LD)] or short days (8:16 LD) for 10 wk, and splenic NE content was determined. In experiment 2, in vitro splenocyte proliferation in response to mitogenic stimulation (concanavalin A) was assessed in spleen cell suspensions taken from long- or short-day hamsters in which varying concentrations of NE were added to the cultures. In experiment 3, splenocyte proliferation was examined in the presence of NE and selective alpha- and beta-noradrenergic receptor antagonists (phenoxybenzamine and propranolol, respectively) in vitro. Short-day animals had increased splenic NE content compared with long-day animals. Long-day animals had higher proliferation compared with short-day animals independent of NE. NE (1 microM) further suppressed splenocyte proliferation in short but not long days. Last, NE-induced suppression of proliferation in short-day hamsters was blocked by propranolol but not phenoxybenzamine. The present results suggest that NE plays a role in photoperiodic changes in lymphocyte proliferation. Additionally, the data suggest that the effects of NE on proliferation are specific to activation of beta-adrenergic receptors located on splenic tissue. Collectively, these results provide further support that photoperiodic changes in immunity are influenced by changes in SNS activity.

Animals↗

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↗

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↗

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↗