Bisnauthsing, Hemlata
(2019)
The molecular impact of physical exercise on a rodent model of schizophrenia: hippocampal gene expression and miRNA levels.
MRes thesis, University of Nottingham.
Abstract
Exercise is known to have positive attributions for humans, and many studies have examined the benefits of physical activity on the human physique and mentality as well as improvements in cognitive function and memory. Various studies on schizophrenia – a psychotic disorder – have shown downregulation in the expression of specific genes in the brain (e.g. GRIN2A, GRIN2B, COMT, DICS1, Egr1, NTrK2, PV, RELN and GAD-1). Studies have examined the manner in which physical activity can influence the expression of specific genes, but very little is known about the effect of physical exercise on the changes in gene expression in patients with schizophrenia.
This study hypothesized that there are effects of exercise on the hippocampal expression of selected genes and miRNAs (miR137, miR132 and miR212) in a rat model of schizophrenia. For this purpose, a phencycline (PCP) model of schizophrenia was used in adult female rats. In two studies, rats were divided into four groups; control rats (no exercise, n = 10), exercised rats (daily wheel running, saline injection, n = 10), schizophrenia model (PCP injection, no exercise, n = 10) and schizophrenia with exercise (PCP injection + wheel running, n = 10). Five rats in each group were humanely killed 6 weeks after PCP/saline injection, and the remaining rats were kept for a further two weeks without access to the running wheel in order to determine whether any changes in gene expression were maintained after the exercise was stopped. Hippocampal gene expression levels for COMT, NTrK2, GRIN2A, GRIN2B, RELN, Erg1, PVALB and DISC1 and miRNAs miR-132, miR-212 and miR-137 were quantified through qPCR.
The results indicate that there were no statistically significant differences in the expression of any of these genes and miRNAs in animals treated with PCP (compared to saline injected) or animals that exercised (compared to sedentary). Similarly, no significant differences were found after a period when the animals had no access to wheel running exercise.
Thus, based on the results, it can be concluded that neither PCP, the combination (exercise and PCP) nor exercise had a significant effect on specific gene or miRNA levels in the rat dorsal hippocampus. This could be due to the fact that the number of animals per group (n= 5) was low, and the experiment came with a lot of limitation.
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