Multiple 5'-splice variants of the rat glutamate transporter-1.

In most brain areas, uptake of extracellular glutamate predominantly occurs through the glutamate transporter subtype, glutamate transporter-1 (GLT-1), which is enriched in astroglia. Here, we report the identification of five splice variants of the 5'-leader sequence of rat GLT-1 which contain varying numbers of upstream open reading frames and encode putative GLT-1 proteins with two distinct N-terminal modifications. We further demonstrate that the identified rat 5'-GLT-1 splice variants are expressed in a brain region-specific manner.

Endothelins negatively regulate glial glutamate transporter expression.

Glutamate is the main excitatory neurotransmitter in the mammalian central nervous system which at high extracellular levels leads to neuronal over-stimulation and subsequent excitotoxic neuronal cell death. Both the termination of glutamatergic neurotransmission and the prevention of neurotoxic extracellular glutamate concentrations are predominantly achieved by the uptake of extracellular glutamate into astroglia through the high-affinity glutamate transporters, excitatory amino acid transporter-2/glutamate transporter-1 (EAAT-2/GLT-1) and EAAT-1/glutamate aspartate transporter (GLAST). Although several injury-induced growth factors such as epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) potently stimulate the expression of glutamate transporters in cultured astroglia, GLT-1 and/or GLAST expression temporarily decreases during acute brain injuries eventually contributing to secondary neuronal cell death.

Chronic endothelin exposure inhibits connexin43 expression in cultured cortical astroglia.

Severe brain lesions are accompanied by sustained increases in endothelin (ET) levels, which in turn profoundly affect brain microcirculation and neural cell function. A known response of astrocytes to acute increases in ET levels is the rapid and transient closure of gap junctions and the subsequent decrease of gap junction-mediated intercellular communication (GJIC). Because evidence exists that the loss of GJIC alters astrocytic gene expression, we analyzed the effects of chronic ET exposure on astrocytic gap junction coupling.

Regulation of glial glutamate transporter expression by growth factors.

Injuries to the brain result in the decline of glial glutamate transporter expression within hours and a recovery after several days. One consequence of this disturbed expression seems to consist in the temporary accumulation of toxic extracellular glutamate levels followed by secondary neuronal cell death. Whereas evidence exists that the decline in glutamate transporter expression results from a loss of neuronal PACAP influences on astroglia, the mechanism(s) inducing the reexpression of glial glutamate transporters is presently unknown.