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Can J Physiol Pharmacol ; 101(5): 244-257, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36988119

ABSTRACT

Alzheimer's disease (AD) is a worldwide chronic progressive neurodegenerative disease. We aimed to investigate and compare the neuroprotective impact of acetyl-l-carnitine and caloric restriction (CR) on AlCl3-induced AD to explore the pathogenesis and therapeutic strategies of AD. Sixty-seven adult male Wistar rats were allocated into Control, AlCl3, AlCl3-acetyl-l-carnitine, and AlCl3-CR groups. Each of AlCl3 and acetyl-l-carnitine were given by gavage in a daily dose of 100 mg/kg and CR was conducted by giving 70% of the daily average caloric intake of the control group. Rats were subjected to behavioral assessment using open field test, Y maze, novel object recognition test and passive avoidance test, biochemical assay of serum phosphorylated tau (pTau), hippocampal homogenate phosphorylated adenosine monophosphate-activated protein kinase, Beclin-1, Bcl-2-associated X protein, and B cell lymphoma 2 (Bcl2) as well as hippocampal Ki-67 and glial fibrillary acidic protein immunohistochemistry. AlCl3-induced cognitive and behavioral deficits coincident with impaired autophagy and enhanced apoptosis associated with defective neurogenesis and defective astrocyte activation. Acetyl-l-carnitine and CR partially protect against AlCl3-induced behavioral, cognitive, biochemical, and histological changes, with more ameliorative effect of acetyl-l-carnitine on hippocampal apoptotic markers, and more obvious behavioral and histological improvement with CR.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Rats , Male , Animals , Aluminum Chloride/adverse effects , Rats, Wistar , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Acetylcarnitine/pharmacology , Acetylcarnitine/therapeutic use , Acetylcarnitine/metabolism , Astrocytes/metabolism , Caloric Restriction , Neurodegenerative Diseases/metabolism , Hippocampus , Apoptosis , Autophagy/physiology , Neurogenesis , Disease Models, Animal
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