CYTOKINES ARE INCREASED IN THE RAT HIPPOCAMPUS AFTER SEROTONERGIC NEURON DEGENERATION AND UP-REGULATE THE EXPRESSION OF GDH, AN ENZYME INVOLVED IN GLUTAMATE DETOXIFICATION
H. Hardinpouzet et al., CYTOKINES ARE INCREASED IN THE RAT HIPPOCAMPUS AFTER SEROTONERGIC NEURON DEGENERATION AND UP-REGULATE THE EXPRESSION OF GDH, AN ENZYME INVOLVED IN GLUTAMATE DETOXIFICATION, Journal of neuroimmunology, 69(1-2), 1996, pp. 117-122
The degeneration of serotonergic neurons increases the expression of g
lutamate dehydrogenase (GDH) in hippocampal astrocytes. This process w
as demonstrated to be independent of the serotonin level. At the same
time, upregulation of tumor necrosis factor (TNF) alpha and interleuki
n (IL)-1 alpha mRNA were observed, whereas levels of transforming grow
th factor (TGF) beta 1 mRNA remained unchanged. The level of GDH mRNA
was increased in primary cultures of hippocampal astrocytes treated wi
th TNF alpha and IL-1 alpha suggesting that these cytokines act on the
GDH metabolism. TNF alpha and IL-1 alpha induced an increase in GDH p
romoter activity in C8S (an astrocytic cell line) transfected with con
structs containing 5' flanking genomic sequences of GDH driving the ex
pression of a reporter gene. These observations suggest that cytokines
may be signals that upregulate the astrocytic GDH expression in respo
nse to the degeneration of serotonergic terminals in the hippocampus.