High levels of histidine decarboxylase in the striatum of mice and rats

Abstract

The neurotransmitter histamine is produced in the tuberomamillary nucleus of the posterior hypothalamus; these neurons project broadly throughout central nervous system. Histidine decarboxylase (HDC) synthesizes histamine from histidine; in the brain, its mRNA is expressed exclusively in the posterior hypothalamus. Histamine receptors are expressed throughout the forebrain, including in cortex, hippocampus, and basal ganglia, suggesting functional innervation of these structures. We investigated the distribution of HDC protein in dissected tissue from mouse and rat, anticipating that it would reflect the density of hypothalamic histaminergic axonal projections and thus qualitatively parallel the known distribution of histamine receptors. HDC protein was found at high levels in hypothalamus, as anticipated. Surprisingly, it was found at comparably high levels in mouse striatum. HDC protein was 10-fold lower in cortex, hippocampus, and cerebellum. Specificity of HDC detection by Western blot was confirmed using HDC knockout mice. Similar high levels of HDC protein were found in dissected striatum from rat. Striatum does not, however, contain comparably elevated of histamine, relative to other forebrain structures; we confirmed this fact using HPLC. This discrepancy between HDC protein and histamine levels in the striatum suggests that histamine metabolism and neurotransmission in basal ganglia may have unique characteristics, the details of which remain to be elucidated.