Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain.
Neurobiol Learn Mem
; 155: 379-389, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30195050
ABSTRACT
Viral infection during early stage of life influences brain development and results in several neurodevelopmental disorders such as schizophrenia, autism and behavioral abnormalities. However, the mechanism through which infection causes long-term behavioral defects is not well known. To elucidate this, we have used synthetic polyinosinic-polycytidylic acid [poly (IC)] which acts as a dsRNA molecule and interacts with toll-like receptor-3 (TLR-3) of microglia cells to evoke the immune system, thus mimicking the viral infection. Rat pups of postnatal day (PND) 7 were infused with a single dose of poly (IC) (5â¯mg/kg BW) and vehicle alone to controls. When these pups grew to 3, 6 and 12â¯weeks, their spatial and fear conditioning memory were impaired as assessed by Morris water maze and passive avoidance test, respectively. We checked the immune activation by staining of TNF-α in the hippocampus and observed that poly (IC) exposure elevated the number of TNF-α positive cells immediately after 12â¯h of infusion in one week rat and it persisted up to postnatal age of 3 and 12â¯weeks. Moreover, poly (IC) significantly decreased the binding of 3H-QNB to the cholinergic receptors in the frontal cortex and hippocampus of 3 and 6â¯weeks rats as compared to control but did not change significantly in 12â¯weeks rats. RT-PCR and immunoblotting results showed that poly (IC) exposure upregulated the expression of memory associated genes (BDNF, Arc, EGR1) at mRNA and protein level in frontal cortex and hippocampus of 3â¯weeks rats as compared to control. However, long-time persistence of poly (IC) effects significantly decreased the expression of these genes in both brain regions of 12â¯weeks rats. Taken together, it is evident that early life exposure to poly (IC) has a long-term effect and impairs learning and memory, probably through TNF-α mediated neuroinflammation and alteration in the expression of memory associated genes in frontal cortex and hippocampus of rats.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Aprendizagem Espacial
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Memória
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Plasticidade Neuronal
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Learn Mem
Ano de publicação:
2018
Tipo de documento:
Article