摘要:

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 melatonin codes day length information. Short day lengths enhance several aspects of immune function in laboratory studies, and melatonin appears to mediate many of the enhanced immunological effects of photoperiod. Generally, field studies report compromised immune function during the short days of autumn and winter. The conflict between laboratory and field data is addressed with a multifactor approach. The evidence for seasonal fluctuations in lymphatic tissue size and structure, as well as immune function and disease processes, is reviewed. The role of pineal melatonin and the hormones regulated by melatonin is discussed from an evolutionary and adaptive functional perspective. Finally, the clinical significance of seasonal fluctuations in immune function is presented. Taken together, it appears that seasonal fluctuations in immune parameters, mediated by melatonin, could have profound effects on the etiology and progression of diseases in humans and nonhuman animals. An adaptive functional perspective is critical to gain insights into the interaction among melatonin, immune function, and disease processe

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00184.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Influences of season and of temperature, photoperiod, and subcutaneous melatonin infusion on glomerular filtration rate (GFR) were measured in ewes. There was a seasonal difference of GFR between summer (June‐August) and winter (December‐February) in Tokyo (35°, 35°N); GFR was significantly (P<0.05) higher in summer (4.2 ± 0.3 ml/ min/kg) than in winter (3.0 ± 0.2 ml/min/kg). GFR was measured after exposure to three types of photoperiod, 24L: 0D, 12L: 12D, and 0L: 24D, for 7 to 8 days. The value for GFR obtained at 20°C was significantly lower (P<0.05) with 0L: 24D than with the other two photoperiodic conditions. GFR obtained during subcutaneous melatonin infusion (20μg/hr for 16 hr/ day for 7 days) with 24L: 0D conditions was significantly (P<0.05) lower (2.5 ± 0.1 ml/min/kg) than without infusion (3.8 ± 0.3 ml/ min/kg) and was about the same as that obtained in animals under 0L: 24D conditions. At 30°C, GFR exhibited no difference between the 3 photoperiodic conditions and was always lower than that found at 20°C. Possible influences of melatonin on GFR

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00185.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:2‐(125I)iodomelatonin binding has been mapped and characterized in the brain and pituitary of the male laboratory rat using quantitative in vitro autoradiography. Specific binding was defined as that completely displaced in the presence of 1 μM melatonin. In the brain high levels of binding were localized over the suprachiasmatic nucleus (SCN), the area postrema (AP), and the spinal tract of the trigeminal nerve (Sp5). Lower densities of binding were found over the medial preoptic area (MPA), the septohypothalamic nuclei (SHy), the anterior hypothalamic area (AHA), the nuclei of the lateral olfactory tract (LOT), the paraventricular (PV), anteroventral (AV) and intermediodorsal (IMD) nuclei of the thalamus, the medial region of the lateral habenular (Lhb), the nuclei of the stria medullaris (SM), the basolateral (BL) and medial (ME) amygdaloid nuclei, the ventromedial nuclei (VMH), the arcuate nuclei (Arc), the subiculum of the hippocampus (S) and the lateral mammillary nuclei (LM). High levels of binding were also present over the pars tuberalis of the pituitary (PT) and the anterior and posterior cerebral arteries (CA). In both neuronal and non‐neuronal areas, specific binding was time dependent and partially reversible in the presence of 1 μM melatonin. Binding was also saturable and of high affinity with dissociation constants (Kd) in the low picomolar range and was significantly inhibited in the presence of 104M guanosine 5′‐0‐(3‐thiotriphosphate) (GTPγS) and 150 mM NaCl in all regions examined, indicating the presence of high affinity G‐protein coupled mel

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00186.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Recently, melatonin was found to be the most potent physiological free radical scavenger known to date. In this work, we attempted to define the role this neurohormone plays in the regulation of apoptosis, since the effect ofbcl‐2, the main gene implicated in its inhibition, acts via an antioxidant mechanism. We investigated the role of melatonin in cell death of thymus, a well known model for the study of apoptosis. Two sets of experiments were carried out: in vivo experiments, performed with Wistar rats, and in vitro experiments, performed with primary cultures of young Wistar rat thymocytes treated with glucocorticoids in order to induce apoptosis. Morphometrical studies in semithin sections of thymus and analysis of DNA fragmentation by gel electrophoresis show that physiological apoptosis occurring in thymus of 65 days old rats, is prevented by the daily administration of melatonin beginning when the rats were 25 days old. Also, we found that at a concentration of 10−7M, melatonin decreases by 35% the percentage of apoptotic cells induced by glucocorticoids in cultured thymocytes of 25 day old rats. 10−9M melatonin decreases cell death by 20%. Finally, melatonin at 10−11Mdid not have any effect. Several hypothesis are discussed to explain this effect: direct interaction of melatonin with glucocorticoid receptors in the thymus; induction of interleukin‐4 release; direct genomic action modulating the expression of apoptosis‐inhibiting genes; an effect on nitric oxide synthase; and finally, the antioxidant action of melatonin. Since apoptosis is a possible mechanism involved in neuronal death shown in several neurodegenerative diseases such as Parkinson or Alzheimer's diseases, investigative efforts should be directed to the possible role of melatonin in inhibiting cell death in tissues other that the thymus. Melatonin might be a potent therapeutic agent in some of these

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00187.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Melatonin is an excellent free radical scavenger, reacting with ferf‐butoxyl and cumyloxyl radicals with rate constants of 3.4 × 107and 6.7 × 107M−1s−1, respectively. Reaction with benzophenone triplet occurs with a near‐diffusion‐controlled rate constant of 7.6 × 109M−1s−1in acetonitrile and probably involves charge transfer. When the radical pair formed by reaction of benzophenone triplet and melatonin is sequestered in a micelle, it is subject to extensive magnetic field effects that can be readily interpreted by the ra

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1995.tb00188.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY