Age and Strain Comparisons of Neurotransmitter Synthetic Enzyme Activities in the Mouse

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Abstract
Activities of the neurotransmitter synthetic enzymes, choline acetyltransferase (EC 2.3.1.6; ChAT), glutamic acid decarboxylase (EC 4.1.1.15; GAD), and tyrosine hydroxylase (EC 1.14.3.2; TH), were assayed in four brain regions of A/J and C57BL/6J mice at three ages (4. 18, and 24 months). The brain regions assayed were the fronto-parietal cortex, hippocampus, striatum, and cerebellum. Strain effects: In some brain regions, at several ages, ChAT activity did not differ among the two srains. However, ChAT was higher in the C57BL/6J strain in the cortex at 18 months, the hippocampus at 18 and 24 months, the striatum at 24 months, and the cerebellum at 4 months. The reverse was true in the cerebellum at 24 months, where ChAT was higher in A/J mice. GAD activity in C57BL/6J mice compared to that of A/J mice was higher in the striatum and cortex, and lower in the hippocampus and cerebellum. TH activities in all four regions were generally higher in C57BL/6J mice than in A. J mice. Age effects: Age differences in enzyme activities varied with the genetic strain. ChAT activity generally was higher in brain regions of older mice of both strains. GAD activity was lower in some brain regions of older mice compared to those of younger mice (A/J striatum, C57BL/6J cortex), but higher in other brain regions of older mice compared to those in younger mice (C57BL/6J striatum, hippocampus of both strains). Whereas there were no age-related differences in striatal TH in either strain, TH activity was higher in other brain regions of older mice (A/J cortex, cerebellum and hippocampus; C57BL/6J cerebellum). In C57BL/6J mice, cortical TH was higher at 18 months than at 4 months, but lower at 24 months than at 18 months. Higher activities of hippocampal ChAT and GAD and cerebellar TH in older C57BL/6J mice reflected increases in Vmax, with no age differences in Km values for substrates. These findings indicate that neurochemical profiles as well as the effects of age on these profiles vary with genetic strain.