Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain

• Published in: Neurobiology of learning and memory Vol. 155; pp. 379 - 389
• Main Authors: Baghel, Meghraj Singh, Singh, Brijendra, Dhuriya, Yogesh Kumar, Shukla, Rajendra Kumar, Patro, Nisha, Khanna, Vinay Kumar, Patro, Ishan Kumar, Thakur, Mahendra Kumar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2018
• Subjects: Developmental neurological disorder; Memory; Poly (I:C); Synaptic proteins; TNF-α; Poly (I:C); TNF-α; Developmental neurological disorder; Memory; Synaptic proteins
• ISSN: 1074-7427; 1095-9564; 1095-9564
• DOI: 10.1016/j.nlm.2018.09.005

•Early life poly (I:C) exposure impaired spatial and fear conditioning memory in 3, 6 and 12 weeks rats.•It elevated TNF-α expression in CA1 and DG at early phase of infection and persisted upto 12 weeks.•It decreased 3H-QNB binding to cholinergic receptor in frontal cortex and hippocampus of 3 and 6 weeks rats but recovered at 12 weeks.•It upregulated expression of BDNF, Arc and Egr1 in frontal cortex and hippocampus of 3 weeks, but downregulated in 12 weeks rats. 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 (I:C)] 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 (I:C) (5 mg/kg BW) and vehicle alone to controls. When these pups grew to 3, 6 and 12 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 (I:C) exposure elevated the number of TNF-α positive cells immediately after 12 h of infusion in one week rat and it persisted up to postnatal age of 3 and 12 weeks. Moreover, poly (I:C) significantly decreased the binding of 3H-QNB to the cholinergic receptors in the frontal cortex and hippocampus of 3 and 6 weeks rats as compared to control but did not change significantly in 12 weeks rats. RT-PCR and immunoblotting results showed that poly (I:C) exposure upregulated the expression of memory associated genes (BDNF, Arc, EGR1) at mRNA and protein level in frontal cortex and hippocampus of 3 weeks rats as compared to control. However, long-time persistence of poly (I:C) effects significantly decreased the expression of these genes in both brain regions of 12 weeks rats. Taken together, it is evident that early life exposure to poly (I:C) 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.