Neurochemical and metabolic consequences of elevated cerebrospinal fluid quinolinic acid concentrations in rat brain.
Quinolinic acid (QUIN) is an endogenous excitatory amino acid, which is elevated in brain tissues or cerebrospinal fluid (CSF) in several acute and chronic inflammatory central nervous system (CNS) diseases. The functional significance of this elevation is unknown but speculations of excitotoxicity have been raised. We have begun to address the pathologic consequences of elevated CSF QUIN by studying the effects of intracerebroventricular (i.cv) administration of QUIN on regional choline acetyltransferase (ChAT) activity, somatostatin content and glucose metabolism in the rat brain. QUIN (12 and 60 nmol) i.cv administration once a day for 7 days (total dose; 84 and 420 nmol, respectively) had minimal effect on somatostatin content and no effect on ChAT activity. In contrast, following continuous i.cv infusion of QUIN for 14 days using an osmotic minipump (480 nmol), ChAT activity dropped in the hippocampus and the striatum and somatostatin content was reduced in the frontal cortex, hippocampus, striatum and amygdala. Moreover, following the QUIN infusion, glucose utilization decreased in the basal nucleus of Meynert, frontal cortex, and portions of the basal ganglia and the limbic system. These results indicate that subchronic i.cv infusion of QUIN to rats results in selective regional neurochemical and metabolic changes distributed throughout the CNS. These results suggest target brain areas and transmitter systems which may be associated with neurologic syndromes characterized by elevated CSF QUIN levels.
Maeda
K
K
Maryland Psychiatric Research Center, University of Maryland, Baltimore 21228, USA. maeda@hiabcd.go.jp
Kaneda
H
H
Whetsell
W O
WO
Tamminga
C A
CA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism
D013004:Somatostatin; D002795:Choline O-Acetyltransferase; D017378:Quinolinic Acid; D005947:Glucose