Long-term treadmill exercise upregulated hippocampal learning-related genes without improving cognitive behaviour in socially isolated rats

Background: Some environment enrichments such as exercise has been reported to improve the diminished cognitive functions and related gene expression. Therefore, we aimed to investigate the effects of prolonged treadmill exercise on long-term learning and hippocampal gene expression, which involves learning and plasticity. Materials and methods: Male Wistar rats (n = 32) randomly assigned into four groups: control (C), social isolation (SI), exercised (E), social isolation + exercise (SE) during postnatal days (PNDs) 21-34. Social isolation protocol was applied during 14 days by placing the rat alone in a cage. Rats were exercised daily, 5 days per week, for overall 4 weeks. Finally, learning performance was evaluated by the novel object recognition test. At the end of learning test, the rats were decapitated to isolate hippocampus tissues for learning related gene expression such as N-methyl-d-aspartate receptor (NMDAR) subunit genes (Grin1, Grin2a, Grin2b) and cyclin dependent kinase 5 (Cdk5), Cdk5 regulatory subunit p35 (Cdk5r), activity-regulated, cytoskeletal-associated protein (Arc), the immediate early gene (c-Fos, a marker of neuronal activation), doublecortin (DCX), achaete-scute homolog 1 (ASCL1), brain-derived neurotrophic factor (BDNF) by real-time polymerase chain reaction (RT-PCR). Results: Grin1, NMDAR subunit gene expression was increased significantly in E group compared to other groups. Grin2b, NMDAR subunit gene expression was increased in E group compared to the SI group. Cdk5 level increased in E group compared to the SE group. The ASCL1 gene expression increased in E group compare to the SE group. The DCX gene expression increasing in C group compared to SI and SE groups. Conclusions: Taken together these findings may point out that long-term social isolation down-regulated learning-related genes. However, treadmill exercise together with social isolation did not restore this down-regulation although treadmill exercise increased learning-related genes without improving cognitive behaviour.