Anti-Apoptotic Effect of Thymoquinone and Intermittent Fasting on the Hippocampus in A Rat Model of Alzheimer’s Disease: A Histological and Immunohistochemical Study

Abstract

Alzheimer's disease (AD) is an age-dependent neurodegenerative condition. Aluminum chloride (AlCl3) is a worldwide neurotoxicant metal which is extensively used in daily life. Thymoquinone (TQ) is the active compound of Nigella Sativa seeds with anti-apoptotic and neuroprotective effects. Intermittent fasting (IF) is a dietary pattern possessing antioxidant and anti-apoptotic qualities that reduce neuroinflammation. The purpose of this study was to evaluate the hippocampal histological and immunohistochemical alterations in adult male albino rats in an experimental model of AlCl3 induced AD and to assess the possible neuroprotective effect of TQ, IF and their combination. In this study, sixty-four adult male albino rats were used. The rats were classified into seven groups: control group, TQ group (oral 50 mg/kg/day), IF group (underwent fasting for 14 hours/day), AL group (oral 300 mg/kg/day AlCl3), AL+TQ group received both AlCl3 and TQ, AL+IF group received AlCl3 and underwent fasting and AL+TQ+ IF group received AlCl3, TQ and underwent fasting. Hippocampal sections were stained by Congo red stain for assessment of amyloid and were immunostained using anti Bax antibodies for assessment of apoptosis. Morphometric and statistical studies were performed. The AL group showed marked hippocampal degenerative changes with amyloid deposition and significant increase in immune expression for Bax marker. These changes were ameliorated in protection groups, especially combination group where degenerative changes, amyloid deposition and Bax immune expression were reduced. In conclusion, aluminum chloride is neurotoxic, both TQ and IF provide potent neuroprotective and anti-apoptotic effects with the best outcome by their combination.