Changes in astrocytic glutamate catabolism enzymes following neuronal degeneration or viral infection

Abstract

Functional changes in astrocytes are among the earliest cellular responses to a wide variety of insults to the central nervous system (CNS). Such responses significantly contribute to maintaining CNS homeostasis. In this context, by controlling energetic metabolism and overall excitability of the CNS, the modulation of glutamate uptake and catabolism in astrocytes is crucial. Here, we review specific modulations of the expression of glutamate cabolizing enzymes (glutamate dehydrogenase and glutamine synthetase) in response to CNS insults (degeneration of serotonergic neurons or viral infection by a human retrovirus, HTLV‐I). The cellular and molecular mechanisms involved in the control of the glutamate catabolism are discussed in relation to neurological disorders. GLIA 21:154–161, 1997. © 1997 Wiley‐Liss, Inc.

Human T-Cell Lymphotropic Virus Type 1-Infected T Lymphocytes Impair Catabolism and Uptake of Glutamate by Astrocytes via Tax-1 and Tumor Necrosis Factor Alpha

“…This activation was characterized by the sustained expression of the proinflammatory cytokine TNF-␣ and upregulation of the gliofilament protein GFAP. These changes in astrocytes produced by infected T lymphocytes are typical of astrocytes engaging a variety of regulatory processes in response to several types of insults (4).…”

“…2B). Glutamate uptake was decreased by treatment with 25 and 50 nM Tax-1 (2,4,8,16, and 24 h) but not with the protein GST alone (113% Ϯ 7% of control value, n ϭ 4). The maximal reduction (63% Ϯ 4% of control value, n ϭ 9, P Ͻ 0.01) (Fig.…”

Protein Kinase C δ (PKCδ) Inhibits the Expression of Glutamine Synthetase in Glial Cells via the PKCδ Regulatory Domain and Its Tyrosine Phosphorylation

“…Changes in GS expression have been associated with human pathology (40), and GS has been reported to protect against neuronal degeneration following trauma or ischemia (20). GS expression has been reported to be regulated by cAMP, glucocorticoids, and insulin (18,19,41).…”

“…GS expression has been reported to be regulated by cAMP, glucocorticoids, and insulin (18,19,41). GS mRNA is regulated by the glucocorticoid response element, NF-B, and by contact with neuronal cultures (40,42,43). Because GS has also been used as an astrocytic marker, understanding of its regulation provides important information on astrocytic differentiation as well as on pathological conditions in the central nervous system.…”

Specific alteration in the expression of glial fibrillary acidic protein, glutamate dehydrogenase, and glutamine synthetase in rats with genetic absence epilepsy

“…The activity of these enzymes is regulated in response to changes in the concentrations of their substrates or products (McKenna et al, 1996), while their expression is differentially regulated under various physiological conditions or after CNS injuries. GDH expression is increased selectively in the hippocampus after serotonergic terminal destruction (Hardin et al, 1994;Belin et al, 1997), while GS activity increases after glutamatergic degeneration (Waniewski and McFarland, 1990). A specific increase in GS expression is seen after paradoxical sleep deprivation (Sallanon-Moulin et al, 1994), while HTLV-1 infection of astrocytes induces GS expression and inhibits that of GDH (Akaoka et al, 1996).…”