Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment--role of brain kynurenic acid.
Journal Article (Journal Article)
Exposure to infections in early life is considered a risk-factor for developing schizophrenia. Recently we reported that a neonatal CNS infection with influenza A virus in mice resulted in a transient induction of the brain kynurenine pathway, and subsequent behavioral disturbances in immune-deficient adult mice. The aim of the present study was to investigate a potential role in this regard of kynurenic acid (KYNA), an endogenous antagonist at the glycine site of the N-methyl-D-aspartic acid (NMDA) receptor and at the cholinergic α7 nicotinic receptor. C57BL/6 mice were injected i.p. with neurotropic influenza A/WSN/33 virus (2400 plaque-forming units) at postnatal day (P) 3 or with L-kynurenine (2×200 mg/kg/day) at P7-16. In mice neonatally treated with L-kynurenine prepulse inhibition of the acoustic startle, anxiety, and learning and memory were also assessed. Neonatally infected mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as adults. Neonatally L-kynurenine treated mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as well as mild impairments in prepulse inhibition and memory. Also, D-amphetamine tended to potentiate dopamine release in the striatum in kynurenine-treated mice. These long-lasting behavioral and neurochemical alterations suggest that the kynurenine pathway can link early-life infection with the development of neuropsychiatric disturbances in adulthood.
Full Text
Duke Authors
Cited Authors
- Liu, X-C; Holtze, M; Powell, SB; Terrando, N; Larsson, MK; Persson, A; Olsson, SK; Orhan, F; Kegel, M; Asp, L; Goiny, M; Schwieler, L; Engberg, G; Karlsson, H; Erhardt, S
Published Date
- February 2014
Published In
Volume / Issue
- 36 /
Start / End Page
- 80 - 89
PubMed ID
- 24140727
Pubmed Central ID
- PMC3947209
Electronic International Standard Serial Number (EISSN)
- 1090-2139
Digital Object Identifier (DOI)
- 10.1016/j.bbi.2013.10.010
Language
- eng
Conference Location
- Netherlands