role of Wnt signaling pathway on the expression of TGF beta1 and TGF beta 2 in cultured rat cortical astrocytes

Astrocytes, the most abundant glia in the central nervous system, modulate neuronal survival and function. Astrocytic functions are mediated by synthesis and secretion of wide ranges of polypeptides through mechanism [s] poorly understood. Among these, TGF beta s are synthesized and released by the astrocytes. In this study, the involvement of Wnt signaling pathway on the synthesis of TGF beta s by the astrocyte was investigated. Cultured rat astrocytes were therefore treated either with Wnt3a [20ng/ml] alone for 24 hours or in combination with sFRP-1 [400 ng/ml] for a further 24 hours. Cells were then harvested and examined for the expression of TGF beta s and the Wnt target gene, cyclin D1. In this study, we were able to show that 1] treatment Wnt3a alone for 24 hours induced the expressions of TGF beta s and cyclin D1; 2] The effect of Wnt was inhibited by pre-treatment with sFRP-1, that is, sFRP-1 pre-treatment significantly blocked the Wnt-induced expressions of TGF beta s and cyclin D1. This study therefore provides the first evidence for the involvement of Wnt signaling pathway in the synthesis of TGF beta proteins by cortical rat astrocytes

Recognition of betaine as an inhibitor of lipopolysaccharide- induced nitric oxide production in activated microglial cells

Neuroinflammation, as a major outcome of microglia activation, is an important factor for progression of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. Microglial cells, as the first-line defense in the central nervous system, act as a source of neurotoxic factors such as nitric oxide [NO], a free radical which is involved in neuronal cell death. The aim of this study was to inhibit production of NO in activated microglial cells in order to decrease neurological damages that threat the central nervous system. An in vitro model of a newborn rat brain cell culture was used to examine the effect of betaine on the release of NO induced by lipopolysaccharide [LPS]. Briefly, primary microglial cells were stimulated by LPS and after 2 minutes, they were treated by different concentrations of betaine. The production of NO was assessed by the Griess assay while cell viability was determined by the MTT assay. Our investigations indicated that LPSinduced NO release was attenuated by betaine, suggesting that this compound might inhibit NO release. The effects of betaine on NO production in activated microglial cells after 24 h were "dose-dependent". It means that microglial cells which were treated with higher concentrations of betaine, released lower amounts of NO. Also our observations showed that betaine compound has no toxic effect on microglial cells. Betaine has an inhibitory effect on NO release in activated microglial cells and may be an effective therapeutic component to control neurological disorders

Effects of intracerebroventricular administration of NGF on blood brain barrier and stress induced protein in the central nervous system

Nerve growth factor [NGF] is the first member characterized of the neurotrophin family. It is known for its crucial role in survival, differentiation and maintenance of neurons both in peripheral and central nervous systems. In addition to its neurotropic role, NGF has also been proposed to act on cells of the immune system. Recent studies show that there is an increased level of NGF in cerebrospinal fluid [CSF] during the acute phase of multiple sclerosis, in animal model of multiple sclerosis and experimental allergic encephalomyelitis [EAE]. In contrast, during the remission phase of the diseases the levels of NGF drop significantly. More recently, the increased level of NGF has also been reported in other autoimmune diseases such as lupus erythematosus. These observations suggest that over production of NGF in CNS may functionally be related to the state of activation of the immune system in autoimmune diseases. Concomitantly, proinflammatory cytokines are upregulated in the acute phase of autoimmune diseases and are known to be potent inducers of the expression of heat shock proteins [HSP]. Moreover, NGF is known to be a chemotactic factor for polymorphonuclear cells [14, 15]. Due to concomitantly increased level of NGF in inflammatory sites and around the blood vessels in acute phase of the disease with leukocyte infiltration of the immune cells in CNS, one may question whether NGF has any effect on production of proinflammatory cytokines through production of heat shock proteins and leukocyte infiltration. To answer the above questions, NGF was injected intracerebroventricularly at doses 20 or 5 micro g/mice for 4 days. The results show that the administered NGF neither has any effect on the expression of HSP-27 nor on leukocyte infiltration in central nervous system, suggesting that the high doses of NGF utilized in these experiments affect neither the immune nor the central nervous systems