DL-alpha-aminoadipic acid (DL-alpha AA), a selective gliotoxic agent produced significant reductions in histamine-N-methyl-transferase (HNMT) and monoamine oxidase-B (MAO-B) activities and an enhancement in histamine (HA) level in the hypothalamus of rats 2 and 4 h after single intracerebroventricular (i.c.v.) or subcutaneous (s.c.) injections of the compound. Histidine decarboxylase (HD) and monoamine oxidase-A (MAO-A) were unaffected after these treatments. Following a single i.c.v. injection of DL-alpha AA of 200 micrograms/rat, or a single s.c. injection of 5 mg/rat, marked diminutions in the astrocytic marker glutamine synthetase (GS) activity occurred suggesting marked glial damage in the hypothalamus. In total, these studies indicate an important role for glial cells in HA metabolism (inactivation).
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