Plasma melatonin, pinealocyte morphology, and surface receptors/antigen expression on macrophages/microglia in the pineal gland following a high‐altitude exposure

Abstract

The present study examined the effects of high-altitude exposure on the pineal gland, the main source of production of melatonin. It was surmised that hypoxia experienced at high altitude, caused by decreased oxygen tension in the ambient air, might lead to some structural alterations in the pineal gland and, hence, affect its melatonin production. Adult Wistar rats were exposed to an altitude of 8,000 m for 2 hr in an altitude chamber and then sacrificed at various time intervals after the exposure. Normal rats kept at ground level were used as controls. Blood samples were collected at various time intervals for measurement of plasma melatonin level, and the pineal glands from both groups were processed for electron microscopy and immunohistochemistry. The plasma melatonin level showed a steady increase following altitude exposure peaking at 7 days and returned to control levels thereafter. Between 1 and 4 days after altitude exposure, the mitochondrial number and lipid droplets in the pinealocytes appeared to be reduced compared with those in control rats. At 7 days, however, the mitochondrial numbers and lipid droplets were noticeably increased. At the same time interval, the expression of complement type 3 receptors and major histocompatibility class II antigens as detected with the antibodies OX-42 and OX-6, respectively, in macrophages/microglia was up-regulated compared with that in the control rats and those killed at earlier times. This was attributed to the increased serum melatonin after the altitude exposure. By 14 and 21 days, the ultrastructure of pinealocytes and immunoreactivity of macrophages/microglia were comparable with those in the control rats. We conclude from this study that an altitude exposure in rats leads to an increase in melatonin production, which returned to control levels with passage of time.

Domoic acid-induced neurotoxicity in the hippocampus of adult rats

“…This activation could be due to a direct effect of melatonin on the microglial cells, as it has been reported that administration of exogenous melatonin upregulates the immune responses (Maestroni et al, 1988). Recently, Kaur et al (2002) have shown that the upregulation of CR3 and MHC II antigen on the microglial cells were coincident with the peak plasma levels of melatonin after altitude exposure. Our study (Ananth et al, 2003b) offers the possibility of potential therapeutic use of melatonin for the prevention of DA-induced neuronal damage.…”

Chronic hypoxia stimulates an enhanced response to immune challenge without evidence of an energetic tradeoff

“…For example, hypoxia temporarily increases circulating levels of melatonin. Melatonin generally leads to increased immune function, especially in laboratory rodents (Frisch et al, 2004;Kaur et al, 2002). Similarly, hypoxia positively influences circulating levels of leptin, a hormone known to be a positive regulator of the immune system (Bernotiene et al, 2006;Fantuzzi and Faggioni, 2000;Grosfeld et al, 2002;Meissner et al, 2005;Shukla et al, 2005).…”

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

“…176,177 Hypoxia exposure of Wistar rats steadily increased plasma melatonin activity to a plateau at seven days. 178 To what extent the beneficial actions of IHT in AD are due to increased release of melatonin by the pineal gland remains to be determined.…”