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PMID: 11157066 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Adaptive plasticity in tachykinin and tachykinin receptor expression after focal cerebral ischemia is differentially linked to gabaergic and glutamatergic cerebrocortical circuits and cerebrovenular endothelium.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 3 ·2001-02-01 ·Pages 798-811

Stumm R, Culmsee C, Schafer MK, Krieglstein J, Weihe E

Abstract

To test the hypothesis of an involvement of tachykinins in destabilization and hyperexcitation of neuronal circuits, gliosis, and neuroinflammation during cerebral ischemia, we investigated cell-specific expressional changes of the genes encoding substance P (SP), neurokinin B (NKB), and the tachykinin/neurokinin receptors (NK1, NK2, and NK3) after middle cerebral artery occlusion (MCAO) in the rat. Our analysis by quantitative in situ hybridization, immunohistochemistry, and confocal microscopy was concentrated on cerebrocortical areas that survive primary infarction but undergo secondary damage. Here, SP-encoding preprotachykinin-A and NK1 mRNA levels and SP-like immunoreactivity were transiently increased in GABAergic interneurons at 2 d after MCAO. Coincidently, MCAO caused a marked expression of SP and NK1 in a subpopulation of glutamatergic pyramidal cells, and in some neurons SP and NK1 mRNAs were coinduced. Elevated levels of the NKB-encoding preprotachykinin-B mRNA and of NKB-like immunoreactivity at 2 and 7 d after MCAO were confined to GABAergic interneurons. In parallel, the expression of NK3 was markedly downregulated in pyramidal neurons. MCAO caused transient NK1 expression in activated cerebrovenular endothelium within and adjacent to the infarct. NK1 expression was absent from activated astroglia or microglia. The differential ischemia-induced plasticity of the tachykinin system in distinct inhibitory and excitatory cerebrocortical circuits suggests that it may be involved in the balance of endogenous neuroprotection and neurotoxicity by enhancing GABAergic inhibitory circuits or by facilitating glutamate-mediated hyperexcitability. The transient induction of NK1 in cerebrovenular endothelium may contribute to ischemia-induced edema and leukocyte diapedesis. Brain tachykinin receptors are proposed as potential drug targets in stroke.

MeSH Terms
Animals Brain Ischemia/genetics,metabolism,pathology Cerebral Cortex/blood supply,metabolism,pathology Cerebrovascular Circulation Endothelium, Vascular/metabolism Gene Expression Regulation Glutamic Acid/metabolism Infarction, Middle Cerebral Artery/genetics,metabolism,pathology Male Neurokinin B/genetics,metabolism Neuronal Plasticity Protein Precursors/genetics,metabolism RNA, Messenger/metabolism Rats Rats, Long-Evans Receptors, Neurokinin-1/genetics,metabolism Receptors, Neurokinin-3/genetics,metabolism Receptors, Tachykinin/biosynthesis,genetics Substance P/genetics,metabolism Tachykinins/biosynthesis,genetics,metabolism Venules/metabolism,pathology gamma-Aminobutyric Acid/metabolism
Chemicals
Protein Precursors RNA, Messenger Receptors, Neurokinin-1 Receptors, Neurokinin-3 Receptors, Tachykinin Tachykinins preprotachykinin Substance P Glutamic Acid gamma-Aminobutyric Acid Neurokinin B
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Stumm R
Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Clinics of Philipps University Marburg, 35033 Marburg, Germany.
Culmsee C
Schafer M K
Krieglstein J
Weihe E
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-02-01
Pages
798-811
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762313
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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