Abstract
The degeneration of serotonergic neurons increases the expression of glutamate dehydrogenase (GDH) in hippocampal astrocytes. This process was demonstrated to be independent of the serotonin level. At the same time, upregulation of tumor necrosis factor (TNF) a and interleukin (IL)-1α mRNA were observed, whereas levels of transforming growth factor (TGF) β1 mRNA remained unchanged. The level of GDH mRNA was increased in primary cultures of hippocampal astrocytes treated with TNFα and IL-1α suggesting that these cytokines act on the GDH metabolism. TNFa and IL-1α induced an increase in GDH promoter activity in C8S (an astrocytic cell line) transfected with constructs containing 5′ flanking genomic sequences of GDH driving the expression of a reporter gene. These observations suggest that cytokines may be signals that upregulate the astrocytic GDH expression in response to the degeneration of serotonergic terminals in the hippocampus.
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