tetano
Editor, Senior Moderator
Brain Behav Immun. 2013 Oct 16. pii: S0889-1591(13)00509-6. doi: 10.1016/j.bbi.2013.10.010. [Epub ahead of print]
Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment - role of brain kynurenic acid.
Liu X, 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.
Source
Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden.
Abstract
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 x 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.
Copyright ? 2013. Published by Elsevier Inc.
KEYWORDS:
Amphetamine, Immune activation, Kynurenine, Locomotor activity, Microdialysis, Neurodevelopment, Postnatal, Prepulse inhibition, Schizophrenia
PMID:
24140727
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24140727
Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment - role of brain kynurenic acid.
Liu X, 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.
Source
Department of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden.
Abstract
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 x 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.
Copyright ? 2013. Published by Elsevier Inc.
KEYWORDS:
Amphetamine, Immune activation, Kynurenine, Locomotor activity, Microdialysis, Neurodevelopment, Postnatal, Prepulse inhibition, Schizophrenia
PMID:
24140727
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24140727