Ne. Preece et S. Cerdan, METABOLIC PRECURSORS AND COMPARTMENTATION OF CEREBRAL GABA IN VIGABATRIN-TREATED RATS, Journal of neurochemistry, 67(4), 1996, pp. 1718-1725
The metabolic precursors and cerebral compartmentation of the augmente
d GABA pool induced by vigabatrin, an irreversible inhibitor of GABA t
ransaminase, have been investigated by C-13 NMR. Adult rats receiving
rat chow ad libitum were given either drinking water only or drinking
water containing 2.5 g/L vigabatrin for 7 days. Both groups of animals
were infused either with [1,2-C-13(2)]acetate (15 mu mol/min/100 g bo
dy weight), an exclusive precursor of GABA formation through the glial
glutamine pathway, or with [1,2-C-13(2)]glucose (15 mu mol/min/100 g
body weight), a substrate that can produce GABA through the glial glut
amine pathway or by direct metabolism in the neurons. The brains were
frozen in situ, extracted with perchloric acid, and analyzed by C-13 N
MR. In vigabatrin-treated animals [C-13]glutamine, a common intermedia
te for [C-13]GABA synthesis from glucose or acetate, was accumulated t
o similar amounts during infusions with [1,2-C-13(2)]glucose or [1,2-C
-13(2)]acetate. However, [C-13]GABA accumulation was sevenfold higher
during [1,2-C-13(2)]glucose infusions or twofold higher during [1,2-C-
13(2)]acetate infusions. These results show that the direct pathway of
GABA formation by neuronal metabolism of glucose predominates over th
e alternative pathway through glial glutamine. Near-equilibrium relati
onships of the aminotransferases of GABA and aspartate imply that the
observed [C-13]GABA accumulation occurs initially in the neuronal comp
artment.