Neonatal infection with neurotropic influenza A virus affects working memory and expression of type III Nrg1 in adult mice

作者：Asp Linnea; Beraki Simret; Kristensson Krister; Ogren Sven Ove; Karlsson Hakan^*

来源：Brain, Behavior, and Immunity, 2009, 23(6): 733-741.

DOI：10.1016/j.bbi.2009.04.004

• Brain
• Tap1
• Cognition
• Anxiety
• Neuregulin
• Syncytin
• TNF
• IFN
• iNOS
• MHC

Epidemiological studies suggest that early life infections may contribute to the development of psychiatric disorders characterized by cognitive deficits. Here, we studied the effects of a neonatal influenza A/WSN/33 virus infection on locomotor activity, working memory and emotional behavior in adult mice. In addition to wild type mice, immunodeficient (Tap1(-/-)) mice lacking functional CD8( ) T cells, were included in the study to model the potential influence of a genetic deficit relating to virus clearance. Three to four months after the infection, infected Tap1(-/-) mice, but not wild type mice, exhibited deficits in working memory as well as increased rearing activity and anxiety. In the medial prefrontal cortices of these infected Tap1(-/-) mice reduced levels of type III Nrg1 transcripts were observed supporting a role for neuregulin 1 signaling in neuronal circuits involved in working memory. Virus replication, distribution or clearance did not differ between the two genotypes. The lack of CD8( ) T cells, however, appeared to contribute to a more pronounced glia response in Tap1(-/-) than in wild type mice. Thus, the present study suggest that the risk of developing deficits in cognitive and emotional behavior following a CNS infection during brain development is influenced by genetic variation in genes involved in the immune response.

• 出版日期2009-8