Local immune regulation in the central nervous system by substance P vs. glutamate.
The response of parenchymal microglia to interferon-gamma (IFN-gamma) varies across the brain. To ask if local neurochemicals contribute to site-specific control, the influence of substance P (SP) and glutamate was evaluated in brainstem vs. hippocampus. In brainstem, stereotaxic injection of SP increased class II MHC upregulation by IFN-gamma, while a SP receptor antagonist (Spantide I) prevented it. In hippocampus, where the baseline response to IFN-gamma was lower, SP was ineffective, but blocking glutamate enhanced the response in a proportion of rats. Attempts to understand and control immune activity in the CNS should take the local neurochemical environment into account.
McCluskey
L P
LP
Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, USA. lmccluskey@mail.mcg.edu
Lampson
L A
LA
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001933:Brain Stem / Q000276:immunology* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*
D000998:Antiviral Agents; D018691:Excitatory Amino Acid Antagonists; D000949:Histocompatibility Antigens Class II; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P; D018698:Glutamic Acid; C056723:FG 9041; D016291:Dizocilpine Maleate; D007371:Interferon-gamma