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

[Mechanism of lithium's effect on follicular development of the rat ovary]

It has been shown that lithium chloride [LiCl], an effective drug for the treatment of bipolar disorder, has side effects on the female reproductive system. In this study, cellular and histological effects of lithium chloride on the development of ovarian follicles in immature female rats were investigated. To induce ovarian follicular development, twenty-three day old immature female rats were injected with 10 IU of pregnant mare serum gonadotropin [PMSG], followed by four doses of LiCl [250 mg/kg/dose] each injected every 12 hours, starting from the time of the PMSG injection. The rat ovaries were removed 48 hours after the PMSG injection and prepared for histological, immunohistochemical, and DNA laddering studies. Control immature female rats received only PMSG, while sham treated rats received PMSG and physiological serum [lithium vehicle]. Our results showed that in the ovaries of LiCl-treated rats there were neither large antral follicles [800-1000 micro m] nor fewer medium sized follicles [400-800 micro m] but a increased number of atretic follicles compared to those in the control rats. The induction of atresia in the ovaries of LiCl-treated rats was further confirmed by the presence of DNA fragmentation. Looking at the cellular levels, lithium extremely significant [p<0.0001] increased the number of TUNEL-positive cells in the granulosa layer of the antral follicles. Taken together, our results suggest that lithium may decrease folliculogenesis by inducing apoptosis in the antral follicles

Nerve growth factor prevents demyelination, cell death and progression of the disease in experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis [EAE], a demyclinating disease induced in the animals parallels multiple sclerosis in human in several aspects, provides a useful model to investigate multiple sclerosis. In this study, we have therefore used this model to study functions of nerve growth factor [NGF] in EAE. NGF with considerable effects on neuron survival, proliferation and differentiation of the nervous system, is also known to act on cells of the immune system. Simultaneous upregulation of proinflammatory cytokines and increased level of NGF points at possible effects of the nerve growth factor in autoimmune diseases. To investigate roles of NGF in experimental allergic encephalomyelitis in vivo, we therefore decided to apply it intracerebroventricularly at a dose of 0.20 mg/mice prior to the induction of EAE. Our clinical observations showed that in the EAE induced animals who received NGF, severity of the disease was reduced significantly compared to that in saline treated EAE mice. Also neuropathological investigation of spinal cords revealed that in contrast to saline treated EAE mice, no signs of cell death, infiltration and demyelination can be seen in NGF treated EAE mice, suggesting that NGF may have clinical implications in multiple sclerosis

Induction of experimental allergic encephalomyelitis in C57/BL6 mice: an animal model for multiple sclerosis

Basic research on the autoimmune disease multiple sclerosis has been performed mainly on its animal model namely experimental allergic encephalomyelitis. There are many different approaches established to get this model. Despite the existence of many references in literature in this regard, we have been faced with many difficulties generating the model suitable for studying different therapies. After a long time of challenging to get a reliable and replicable method, we came up with the following major points: First, the key element for getting a maximum number of sick animals at a defined time is to consider the most appropriate animal body weight [19-20 gr]. Even though the age of immunized animals [6-8 week old] is highlighted in literature, we found out that body weight is of a greater importance. Secondly, because the only available susceptible mice strain in Iran is C57/BL6, the choice of peptide for immunization would be myelin oligodendrocyte glycoprotein [35-55 sequence of this peptide 200 [micro]g/animal]. Finally, pertussis toxin which is a costly reagent plays a key role in stimulating the immune response. Altogether, we recommend that considering the above mentioned tricks and tracks, one would definitely be able to generate a chronic progressive type of model, for basic research on therapies of multiple sclerosis