Chronic sleep deprivation induces spatial memory impairment, chromatolysis, and histoarchitectural changes in the CA3 region of the hippocampus

Abstract

BACKGROUND AND AIM: Sleep is a vital bodily function involving the activity of brain networks. Disruption in sleep patterns can lead to problems with memory and even changes in brain structure. Hence, this study aimed to assess the effects of chronic sleep deprivation on spatial memory and histopathological changes in the CA3 region of the hippocampus of adult male Wistar rats.

METHODOLOGY: 12 male rats were divided into two groups of six rats each. Group (I) received 2ml/kg of distilled water, while Group II were sleep-deprived for 18 hours daily for 21 consecutive days using the modified multiple platform method. The Morris water maze test was conducted to assess spatial learning and memory. At the end of the experiment, the rats were euthanized using 75mg/kg of ketamine hydrochloride intraperitoneally, and the brain tissues were harvested.  Hippocampal tissue homogenate of some rats were used to assess glutamate levels, whereas, the whole brains of the remaining rats were fixed, and processed using Haematoxylin & Eosin, and Cresyl Fast Violet stains to demonstrate the general histoarchitecture and Nissl substance expression in the hippocampal CA3 regions respectively. Cavalieri’s principle was employed for estimation of the number of pyramidal cells in the CA3 region of the hippocampus of Wistar rats.

RESULTS: There was a significant increase (p<0.001) in the time spent locating the escape platform in the sleep-deprived group compared to the control group in the MWM test. No significant difference (p>0.05) was observed in hippocampal glutamate activity levels when the sleep deprived group was compared with the control group. Histological findings revealed degenerative changes such as cytoplasmic vacuolation, karyorrhexis and pyknosis in the pyramidal cells of the CA3 region of the hippocampus of Wistar rats. Additionally, the number of pyramidal cells in the CA3 region was significantly decreased (p>0.05) in the sleep-deprived group compared to the control. Furthermore, the Nissl substance in the hippocampal sections of the sleep-deprived group exhibited a significant (p>0.05) decrease in staining intensity compared to the control group, suggesting disruptions in neuronal function and protein synthesis.

CONCLUSION: The findings of this study revealed spatial memory impairment, histological alterations, reduced pyramidal cell count, and protein depletion in the CA3 region of the sleep-deprived rats.