Co-administration of coenzyme Q10 and curcumin mitigates cognitive deficits and exerts neuroprotective effects in aluminum chloride-induced Alzheimer's disease in aged mice

Abstract

Aluminum chloride (AlCl 3 ), a known neurotoxic and Alzheimerogenic metal disrupts redox homeostasis which plays a pivotal role in pathophysiology of neurodegenerative disorders, particularly cognitive decline. The current study was designed to unveil the long-term neuroprotective outcomes and efficacy of CoQ10 and curcumin low dose (100 mg/kg each) combination in 18-months old geriatric male Balb/c mice subjected to AlCl 3 -prompted memory derangements (200 mg/kg in water bottles) for 28 days. The neuroprotective properties driven by antioxidant mechanisms were assessed via observing cellular pathology in key-memory related brain regions including the cornuammonis (CA3 and DG) and cortex 2/3 layer. Our outcomes revealed that AlCl 3 exposure significantly reduced spatial learning and memory. In contrast, CoQ10 and curcumin combinatorial regime markedly mitigated cognitive deficits Vs. individual high-dose in AlCl 3 -treated animals as demonstrated by their improved performance in neurobehavioral tests such as the Y-maze, novel object recognition, passive avoidance and Morris-water maze test. Additionally, CoQ10 and curcumin co-administration restored redox balance by significantly reducing the levels of oxidative stressor (MDA) and increasing the anti-oxidant capacity (SOD,GPx). AchE is an enzyme involved in acetylcholine breakdown which negatively impacts acetylcholine levels and memory function. AlCl 3 exposure elevated AchE levels in mice brains vs. treatment. This neurochemical alteration was notably reversed in the dual-treatment group. Furthermore, CoQ10 and curcumin ameliorated AlCl 3 -induced neurotoxicity by preserving neuronal cytoarchitecture in both cortical and hippocampal regions. In conclusion, CoQ10 and curcumin combination might attenuate memory loss induced by AlCl 3 -intoxication via restoring aberrant AchE activity, enhanced anti-oxidant defenses and salvaging the deleterious neuronal damage. The figure was generated with Biorender.com (Agreement number:KH27E9719U; Dated: 7th-October-2024). • Aluminium chloride (AlCl 3 ) exposure significantly disrupts spatial learning and memory in geriatric mice. • CoQ10 and curcumin co-administration effectively halted AlCl₃-induced cognitive decline and improved behavioral parameters. • The combination therapy restored antioxidant balance by reducing MDA levels and boosting SOD and GPx activity. • AlCl₃ increases acetylcholinesterase (AchE) activity, which is normalized by CoQ10 and curcumin dual therapy. • Combination preserved neuronal cytoarchitecture, density and morphology in critical memory-related brain regions.

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