title: Memory and learning seems to be related to cholinergic dysfunction in the JE rat model.
abstract: Cognitive changes have been known in encephalitis but in Japanese encephalitis (JE) such studies are limited. This study aims at evaluating the spatial memory and learning and correlate with markers of cholinergic activity in the brain.12day old Wistar rats were inoculated with dose of 3×10(6)pfu/ml of JE virus. On 10, 33 and 48days post-inoculation (dpi), spatial memory and learning was assessed by Y maze. Brain biopsies from frontal cortex, corpus striatum, hippocampus and cerebellum were taken. Muscarinic cholinergic receptor was assayed by Quinuclidinyl benzylate (H3-QNB) binding, CHRM2 gene expression by real time PCR and choline acetyl transferase (ChAT) by Western blot. Spatial learning and memory showed significant decline in rats inoculated with JEV on 10 and 33dpi (47.5%, p<0.01; 30.2%, p<0.01). It started recovering on 48dpi. Muscarinic cholinergic receptors showed significant decrease in frontal cortex (31%, p=0.001; 26%, p=0.003), hippocampus (57%, p=0.001; 39.9%, p=0.002) and cerebellum (31.2%, p=0.008; 21.6%, p=0.007) but not in corpus striatum as compared to control. The mRNA expression of CHRM2 receptor gene showed significant decrease in the expression in frontal cortex (48%, p<0.001; 38%, p<0.01), hippocampus (43%, p<0.001; 37%, p<0.05) and cerebellum (46%, p<0.001; 42%, p<0.05) on 10 and 33dpi. ChAT showed significant fold decrease in the expression in frontal cortex (2.11, p<0.01, 1.12, p<0.05) and hippocampus (2.2, p<0.01, 1.41, p<0.05) on 10 and 33dpi. Correlation between ChAT, CHRM2 and total muscarinic receptor activity with spatial memory were found at different dpi. There was transient spatial learning and memory impairment which was associated with reduction of total muscarinic receptor binding, CHRM2 gene and ChAT expression in different brain region of rat infected with JE Virus.
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, India.
authors.forename: Prashant Singh
authors.initials: PS
authors.lastname: Chauhan
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, India. Electronic address: drukmisra@rediffmail.com.
authors.forename: Usha Kant
authors.initials: UK
authors.lastname: Misra
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, India.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow, India.
authors.forename: Lalit Pratap
authors.initials: LP
authors.lastname: Chandravanshi
authors.affiliation: Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow, India.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Khanna
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004195:Disease Models, Animal; D018349:Encephalitis Viruses, Japanese / Q000302:isolation & purification; D004672:Encephalitis, Japanese / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D065853:Spatial Learning / Q000502:physiology*
chemical_list: D011976:Receptors, Muscarinic; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: Brain regions; Cognition; Learning; Memory; Muscarinic receptor; Viral encephalitis