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Japanese Encephalitis Virus Infection Results in Transient Dysfunction of Memory Learning and Cholinesterase Inhibition

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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 × 106 pfu/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.

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Acknowledgment

We thank Rakesh nigam and Shakti kumar for secretarial help.

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Authors and Affiliations

  1. Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Science, Raebareily Road, Lucknow, 226014, India

    Prashant Singh Chauhan, Jayantee Kalita & Usha Kant Misra

  2. Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow, India

    Vinay Kumar Khanna

Authors
  1. Prashant Singh Chauhan
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  2. Vinay Kumar Khanna
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  3. Jayantee Kalita
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  4. Usha Kant Misra
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Correspondence to Usha Kant Misra.

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Conflicts of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

The experimental protocol was approved by Institutional Animal Ethics Committee (KGMU/49/IAEC/2013). All the experimental procedures were carried out in accordance with the institutional guidelines laid down by the committee for the purpose of control and supervision of experiments on animal (CPCSEA).

Funding Support

Yes, this study was (No. CST/SERPD/D-996) financially supported by a grant from Uttar Pradesh Council of Science & Technology Lucknow, UP, India.

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Chauhan, P.S., Khanna, V.K., Kalita, J. et al. Japanese Encephalitis Virus Infection Results in Transient Dysfunction of Memory Learning and Cholinesterase Inhibition. Mol Neurobiol 54, 4705–4715 (2017). https://doi.org/10.1007/s12035-016-9963-6

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  • DOI: https://doi.org/10.1007/s12035-016-9963-6

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