Nitric oxide synthase activities are selectively decreased in vulnerable brain regions in thiamine deficiency

Abstract

Pyrithiamine-induced thiamine deficiency in the rat exhibits many neuropathological and biochemical similarities to Wernicke's Encephalopathy in humans. Activities of constitutive nitric oxide synthase (NOS) were measured in vulnerable (thalamus and cerebellum) and non-vulnerable (hippocampus and striatum) brain regions of pyrithiamine-induced thiamine-deficient rats. NOS activities were significantly decreased in the thalamus (by 26%, P < 0.05) of presymptomatic thiamine-deficient rats compared to pair-fed controls. Following onset of symptoms, in addition to thalamus (−38%, P < 0.01), cerebellum (−50%, P < 0.01) also manifested significantly decreased activities of NOS. Hippocampal and striatal activities of NOS were unchanged at both presymptomatic and symptomatic stages of thiamine deficiency. Selectively decreased activities of neuronal NOS in the thalamus and the cerebellum extends the previous observations of region-selective metabolic changes and, ultimately, neuronal cell loss observed in thiamine deficiency.