Memory and learning seems to be related to cholinergic dysfunction in the JE rat model

- Intracerebral inoculation of JEV (3 × 106 pfu/ml) on 12 day Wistar rats.
- Spatial memory and learning was impaired on 10 and 33 dpi and recovered on 48 dpi.
- Cholinergic markers were reduced in cortex, hippocampus, striatum, and cerebellum.
- Correlation between spatial memory and brain cholinergic parameters was found.
- Transient form of spatial memory impairment was observed in JE infected rats.

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.12 day old Wistar rats were inoculated with dose of 3 × 106 pfu/ml of JE virus. On 10, 33 and 48 days 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 33 dpi (47.5%, p < 0.01; 30.2%, p < 0.01). It started recovering on 48 dpi. 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 33 dpi. 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 33 dpi. 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.