Glutamate transport, glutamine synthetase and phosphate‐activated glutaminase in rat CNS white matter. A quantitative study

Abstract

Glutamatergic signal transduction occurs in CNS white matter, but quantitative data on glutamate uptake and metabolism are lacking. We report that the level of the astrocytic glutamate transporter GLT in rat fimbria and corpus callosum was 35% of that in parietal cortex; uptake of [ 3 H]glutamate was 24 and 43%, respectively, of the cortical value. In fimbria and corpus callosum levels of synaptic proteins, synapsin I and synaptophysin were 15-20% of those in cortex; the activities of glutamine synthetase and phosphate-activated glutaminase, enzymes involved in metabolism of transmitter glutamate, were 11-25% of cortical values, and activities of aspartate and alanine aminotransferases were 50-70% of cortical values. The glutamate level in fimbria and corpus callosum was 5-6 nmol/mg tissue, half the cortical value. These data suggest a certain capacity for glutamatergic neurotransmission. In optic and trigeminal nerves, [ 3 H]glutamate uptake was < 10% of the cortical uptake. Formation of [ 14 C]glutamate from [U-14 C]glucose in fimbria and corpus callosum of awake rats was 30% of cortical values, in optic nerve it was 13%, illustrating extensive glutamate metabolism in white matter in vivo. Glutamate transporters in brain white matter may be important both physiologically and during energy failure when reversal of glutamate uptake may contribute to excitotoxicity.

Regional Distribution of Sodium-Dependent Excitatory Amino Acid Transporters in Rat Spinal Cord

“…The importance of the EAAT system in spinal cord white matter is emphasized by (a) the apparent contribution of reversed glutamate transport to excitotoxic-induced white matter apoptosis (11,59), and (b) the fact that glutamate transport inhibitors protect from or decrease white matter pathology (10,11). This confirms previous reports of EAAT immunoreactivity in cervical spinal cord white matter (11,23,60).…”

Expression of neuronal markers, synaptic proteins, and glutamine synthetase in the control and regenerating lizard visual system

“…Interestingly, the abundant and strong GS staining in the lizard ON-OTr is apparently linked to a glutamatergic glial network, as the abundant coexpression of GS/VGLUT1 in glial cells suggests. Consistent with this view, all three isoforms of VGLUTs have been detected in rodent astrocytes (review in Montana et al, 2006); VGLUT3 þ /GS þ rat astrocytes have been described in vitro (Ni and Parpura, 2009); glutamate can be synthesized de novo in astrocytes and released by ON glia in mice (Hamilton et al, 2008;Ni and Parpura, 2009); glutamatergic signal transduction occurs in CNS white matter and peripheral nerves, as revealed by the presence of GS activity in the rat fimbria, corpus callosum, ON, and trigeminal nerves (Hassel et al, 2003), and also in the cat and fish ON (Jennings et al, 2002;Parrilla et al, 2009). The literature about the GS expression and/or activity in the vertebrates nervous system after surgical lesions is contradictory.…”

“…Among them, vesicular glutamate transporter-1 (VGLUT1) is widely expressed in the central and peripheral nervous system of mammals (Gong et al, 2006;Brumovsky et al, 2007), and apparently has a high specificity for the glutamatergic neurons and glia (Brumovsky et al, 2007;Hamilton et al, 2008). Moreover, glutamate serves as a precursor of GABA in neurons and as a metabolic fuel in astrocytes, and is utilized for either glutamine synthesis or the exchange with cystine for glutathione antioxidant production (McKenna et al, 1996;Hassel et al, 2003). After being taken up by glial cells, glutamate is converted into glutamine by the enzyme glutamine synthetase (GS), a functional macroglial marker (Tansey et al, 1991).…”

Carnitine Treatment Inhibits Increases in Cerebral Carnitine Esters and Glutamate Detected by Mass Spectrometry After Hypoxia-Ischemia in Newborn Rats

“…22 The reduction in EAA levels in this study may be associated with prevention of the compromise of neuronal or astrocyte glutamate uptake and metabolism associated with ischemia. 23 Other mechanisms may account for the effects of carnitine. Our results show that treatment with carnitine is associated with reduced superoxide expression after HI.…”