Comparative neuroprotective and exercise capacity effects of prophylactic intermittent fasting and probiotics in sleep-deprived rats: insights into anti-inflammatory marker modulation and CLOCK gene regulation

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Background Prophylactic probiotics and intermittent fasting (IF) substantially modulate the neuropsychological functions and exercise capacity in rats subjected to sleep deprivation (SD). A comparative study was conducted to analyze the effects of probiotics and IF on SD-induced neuropsychological disturbances and compromised muscle endurance. Methods Forty albino Wistar rats were randomly assigned to four groups. The NSD group was maintained on a standard chow diet for 12 weeks. The SD group followed an SD regimen for 72 h per week over 8 weeks, starting from the fifth week. The SDP group received probiotics at a dose of colony-forming units (CFUs)/100 g/day for 4 weeks prior to SD, followed by 8 weeks of concurrent probiotic administration with SD. The SDIF group underwent an alternate-day fasting regimen for 4 weeks before SD, followed by 8 weeks of simultaneous SD combined with IF. Neuropsychological functions and exercise capacity were tested, and then the brains were carefully dissected, sectioned, and processed for hematoxylin and eosin, cresyl violet, and immunohistochemical staining. Results Inflammatory markers, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and hippocampal expression of the circadian locomotor output cycles kaput ( CLOCK ) gene, were significantly elevated in the SD group. Conversely, it showed significant decreases in endurance, exploratory behavior, hippocampal superoxide dismutase (SOD) activity, and fecal short-chain fatty acids (SCFAs). Histological analysis also revealed hippocampal gliosis, apoptosis, CA1 pyramidal cell degeneration, layer disorganization, and upregulation of glial fibrillary acidic protein (GFAP), NF-κB, and cleaved caspase-3. Nevertheless, both probiotics and IF markedly reduced serum MDA, hippocampal CLOCK gene expression, gliosis, and apoptosis and enhanced memory performance. In addition, they significantly increased hippocampal SOD activity and SCFAs. Conclusion These findings indicate that prophylactic probiotics decrease cognitive disruption and impaired muscle endurance caused by SD through CLOCK gene regulation compared to that with IF. This highlights the need for further research to elucidate these mechanisms. Histological findings also supported these results, showing improved neuronal structure in the hippocampus following probiotic treatment.

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