title: Japanese Encephalitis Virus Infection Results in Transient Dysfunction of Memory Learning and Cholinesterase Inhibition.
abstract: Cholinergic system has an important role in memory and learning. Abnormal cognitive and behavioral changes have been reported in Japanese encephalitis (JE), but their basis has not been comprehensively evaluated. In this study, we report memory and learning and its association with acetylcholinesterase (AChE) activity, JE virus titer, and with histopathological observations in a rat model of JE. Wistar rats were intracerebrally inoculated on 12th day with 3 × 106pfu/ml of JE virus. Memory and learning were assessed by the active and passive avoidance tests on 10, 33, and 48 days post inoculation (dpi). After 10, 33, and 48 dpi AChE activity, Japanese encephalitis virus (JEV) titer and histopathological changes were studied in the frontal cortex, thalamus, midbrain, cerebellum, and hippocampus. There was significant impairment in memory and learning on 10 dpi which started improving from 33 dpi to 48 dpi by active avoidance test. Passive avoidance test showed decrease in transfer latency time of retention trial compared to acquisition on first, second, and third retention day trial compared to controls. AChE inhibition was more marked in the hippocampus, frontal cortex, and cerebellum on 10 dpi. However, AChE activity started improving from 33 dpi to 48 dpi. AChE activity in the thalamus and midbrain correlated with active avoidance test on 10 dpi and 33 dpi. Histopathological studies also revealed improvement on 33 and 48 compared to 10 dpi. The present study demonstrates transient memory and learning impairment which was associated with reduction in AChE, JEV titer, and damage in different brain regions of JEV infected rats.
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, 226014, India.
authors.forename: Prashant Singh
authors.initials: PS
authors.lastname: Chauhan
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
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, 226014, India.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, 226014, India. drukmisra@rediffmail.com.
authors.forename: Usha Kant
authors.initials: UK
authors.lastname: Misra
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning; D001921:Brain / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D004664:Encephalitis Virus, Japanese / Q000502:physiology*; D004672:Encephalitis, Japanese / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D008568:Memory; D017208:Rats, Wistar
chemical_list: D000110:Acetylcholinesterase
keywords: Acetylcholinestrase; Brain regions; Cognition; Histopathology; Japanese encephalitis; Memory learning