Local immune regulation in the central nervous system by substance P vs. glutamate

• Published in: Journal of neuroimmunology 2001-06, Vol.116 (2), p.136-146
• Main Authors: McCluskey, Lynnette Phillips, Lampson, Lois A
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - pharmacology; Brain Stem - immunology; Brain Stem - metabolism; Brainstem; Class II MHC; Dizocilpine Maleate - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; g-Interferon; glutamic acid; Glutamic Acid - metabolism; Hippocampus; Hippocampus - immunology; Hippocampus - metabolism; Histocompatibility Antigens Class II - immunology; Interferon-gamma - pharmacology; Interferon-γ; Male; Microglia; Microglia - immunology; Microglia - metabolism; MK-801; Neural–immune interactions; Neuroimmunomodulation - drug effects; Neuroimmunomodulation - physiology; NMDA receptors; Quinoxalines - pharmacology; Rat; Rats; Rats, Inbred F344; Receptors, N-Methyl-D-Aspartate - metabolism; Spantide; substance P; Substance P - metabolism
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(01)00295-8

The response of parenchymal microglia to interferon-gamma (IFN-γ) 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-γ, while a SP receptor antagonist (Spantide I) prevented it. In hippocampus, where the baseline response to IFN-γ 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.