Production, regulation and role of nitric oxide in glial cells.

In neuropathological conditions such as Alzheimer's disease, Parkinson's disease, AIDS dementia complex and multiple selerosis, activation of microglial cells and astroglial cells is evident. Under these neuropathological conditions cellular damage in the brain is considered to arise indirectly from cytotoxic substances produced by activated glial cells. One of these toxins is NO which has been demonstrated to be produced during several neuropathological conditions. High NO levels are produced by glial cells and exert neurotoxic effects. Astroglial cells and microglial cells communicate in various ways to reduce NO production by microglial cells which is essential to maintain homeostasis in the brain. The production of TGFβ by glial cells and its activation by astrocyte-derived tPA represents one mechanism by which astroglia limit NO production in the brain

Involvement of Noradrenergic Transmission in the PVN on CREB Activation, TORC1 Levels, and Pituitary-Adrenal Axis Activity during Morphine Withdrawal

Experimental and clinical findings have shown that administration of adrenoceptor antagonists alleviated different aspects of drug withdrawal and dependence. The present study tested the hypothesis that changes in CREB activation and phosphorylated TORC1 levels in the hypothalamic paraventricular nucleus (PVN) after naloxone-precipitated morphine withdrawal as well as the HPA axis activity arises from α1- and/or β-adrenoceptor activation. The effects of morphine dependence and withdrawal on CREB phosphorylation (pCREB), phosphorylated TORC1 (pTORC1), and HPA axis response were measured by Western-blot, immunohistochemistry and radioimmunoassay in rats pretreated with prazosin (α1-adrenoceptor antagonist) or propranolol (β-adrenoceptor antagonist). In addition, the effects of morphine withdrawal on MHPG (the main NA metabolite at the central nervous system) and NA content and turnover were evaluated by HPLC. We found an increase in MHPG and NA turnover in morphine-withdrawn rats, which were accompanied by increased pCREB immunoreactivity and plasma corticosterone concentrations. Levels of the inactive form of TORC1 (pTORC1) were decreased during withdrawal. Prazosin but not propranolol blocked the rise in pCREB level and the decrease in pTORC1 immunoreactivity. In addition, the HPA axis response to morphine withdrawal was attenuated in prazosin-pretreated rats. Present results suggest that, during acute morphine withdrawal, NA may control the HPA axis activity through CREB activation at the PVN level. We concluded that the combined increase in CREB phosphorylation and decrease in pTORC1 levels might represent, in part, two of the mechanisms of CREB activation at the PVN during morphine withdrawal

Endotoxin-induced appearance of immunoreactive interleukin-1β in ramified microglia in rat brain: A light and electron microscopic study

Interleukin-1 plays an important role as mediator of endotoxin-induced responses in the brain such as fever, sleep, anorexia, behavioural and neuroendocrine changes. In the present study, interleukin-1β immunocytochemistry has been performed at the light and electron microscopic level to study the cellular and subcellular localization of interleukin-1β in the brains of rats given endotoxin or saline. Light microscopic analysis of rats killed 4, 8 or 24 h after endotoxin (2.5 mg/kg) given intraperitoneally or intravenously revealed a region-specific localization of immunoreactive interleukin-1β in macrophages and microglial cells. After saline treatment, no induction of interleukin-1β immunoreactivity occurred in the brain. After administration of endotoxin, many interleukin-1β-positive cells were found in the meninges, choroid plexus, circumventricular organs, cerebral cortex and hypothalamus. The number of interleukin-1β-positive microglial cells reached a maximum 8 h after administration of endotoxin, irrespective of the route of administration. In general, more interleukin-1β-positive microglial cells were found after intravenous than after intraperitoneal administration of endotoxin. Interleukin-1β-positive microglial cells were often grouped in patches in the vicinity of blood vessels. At the surface of the cerebral cortex, in the meninges, intermediate cell forms between interleukin-1β-positive macrophages and microglial cells were found. interleukin-1β-positive perivascular microglia were localized at the brain side of the basal lamina. Immunoreactive interleukin-1β was found at the luminal side of the endothelial cells lining the venules. Furthermore, microglial cells that extended their processes into the ependymal layer of the third ventricle were observed. Results of the electron microscopic studies revealed immunoreactive interleukin-1β in many cells with the cellular characteristics of microglial cells, but also, in some cells, identified as astrocytes. In microglial cells, immunoreactive interleukin-1β was found in the cytoplasm but not in the endoplasmatic reticulum or Golgi apparatus. These results show that after peripheral administration of endotoxin, immunoreactive interleukin-1β is induced in macrophages in the meninges and in the choroid plexus, as well as in microglial cells in parenchyma. Interleukin-1β produced by these cells may serve as a signal for adjacent or more distant targets (neurons, endothelial cells, microglial cells) to play a role in the induction of non-specific symptoms of sickness

Extraneuronal Catecholamine as an Index for Sympathetic Activity: A Scanning Microfluorimetric Study on the Iris of the Rat1

ABSTRACT Schipper