Behavioral and Neurochemical Alterations Following Thiamine Deficiency in Rodents: Relationship to Functions of Cholinergic Neurons

Abstract

Memory deficits are induced during the late stage (20-25 days) of thiamine-deficient (TD) feeding. In this review, the role of cholinergic neurons on the memory deficit induced by TD feeding are summarized. Although memory deficit cannot be suppressed by an injection of thiamine once it appears, such impairment was found to be protected by early treatment with thiamine during TD feeding. Administration of muscarinic M(1) agonist McN-A-343 reversed the memory deficit observed in TD mice, although the muscarinic M(2) antagonist methoctramine did not. The "kampo" (traditional herbal) medicine, "kami-untan-to" (KUT), protected against the memory deficit observed in TD mice. Choline acetyltransferase (ChAT) fluorescence intensity, a marker of presynapse of cholinergic neurons, was decreased in the cortex and hippocampus at an early stage (14th day) of TD, and it was decreased in a wide range of brain areas at a late stage (25th day) of TD. Early KUT treatment inhibited the reduction of ChAT in the hippocampus of TD mice. These findings suggested that the memory deficit may be caused by a reduction in the cholinergic function at an early stage of TD, and that the activation of cholinergic neurons may play an important role in the improvement of TD-induced memory deficit.