Induction of the kynurenine pathway by neurotropic influenza A virus infection.
Glutamatergic NMDA (N-methyl D-aspartate) receptors play a critical role in brain development and neurotransmission. Kynurenic acid, an end product of tryptophan degradation along the kynurenine pathway, is an endogenous NMDA receptor antagonist. In the present study, the effects of neurotropic influenza A virus infection on the kynurenine pathway were investigated in mouse brain primary cell cultures and in mouse brain after infection on day 3 of postnatal life. Altered levels of transcripts encoding several key enzymes of the kynurenine pathway were observed in infected neuron and glial cell cultures. In vivo, changes in the levels of such transcripts in brain were observed on postnatal days 7 and 13 but not on day 24. On postnatal day 13, infiltrating T lymphocytes and increased levels of kynurenic acid were observed in the brains of the infected animals. Taken together, the present results indicate that central nervous system infections during early life can activate the entire kynurenine pathway. Such activation is likely to result in the generation of several bioactive metabolites, as supported by our finding of a transient increase of kynurenic acid. In light of its antagonistic actions on the NMDA receptor, kynurenic acid can potentially link infections with glutamatergic signaling in the developing brain.
Holtze
Maria
M
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Asp
Linnéa
L
Schwieler
Lilly
L
Engberg
Göran
G
Karlsson
Håkan
H
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018920:Coculture Techniques; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D018698:Glutamic Acid / Q000378:metabolism; D009980:Influenza A virus / Q000378:metabolism*; D007736:Kynurenic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012559:Schizophrenia / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D012701:Serotonin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D018698:Glutamic Acid; D007736:Kynurenic Acid