Protective Role of Caloric Restriction versus L-Carnitine on Aluminium Chloride Induced Cognitive Deficit in Rats

Abstract

Abstract Introduction Alzheimer’s disease (AD) is a worldwide chronic progressive neurodegenerative disease. However, its pathophysiology is still unclear and there is no determined cure for it up till now. Both Acetyl-L-carnitine (ALCAR) and caloric restriction (CR) slow down the aging process. Hypothesis To compare the neuroprotective impacts of ALCAR and CR on aluminum chloride (AlCl3) induced AD in adult male rats to explore the pathogenesis and therapeutic strategies of AD. Materials and Methods Our study was carried out on 67 adult male albino rats that were allocated into 4 groups: Control, AlCl3, AlCl3-Acetyl-L-Carnitine and AlCl3-Caloric Restriction groups. AlCl3 and ALCAR were taken by gavage in a dose of 100 mg/1ml/kg. B.W. and CR was done by 70% of the daily average caloric intake of the control group for 30 days. All rats were subjected to behavioral assessment; open field test (OFT), Y maze, novel object recognition test (NORT) and passive avoidance test (PAT), biochemical assay of serum phosphorylated tau (pTau), hippocampal homogenate phosphorylated adenosine monophosphate kinase (pAMPK), Beclin-1, Bax (Bcl-2-associated X protein), Bcl2 (B-cell lymphoma-2) and Bax/Bcl2 ratio as well as hippocampal histological studies using H&E, Silver stain and Immunohistochemistry (nuclear protein Ki 67 & glial fibrillary acidic protein GFAP). Results The results showed cognitive and behavioral deficits induced by AlCl3 and this were coincident with increased level of serum pTau, aggregated neurofibrillary tangles (NFTs) and senile plaques with increased pAMPK. impaired autophagy and enhanced apoptosis associated with defective neurogenesis and defective astrocyte activation. Conclusion ALCAR and CR partially improved the AlCl3 induced behavioral, cognitive, biochemical and histological changes, with more ameliorative effect of ALCAR on hippocampal apoptotic markers, with more obvious behavioral and histological improvement with CR.