Therapeutic Effect of Vitamin D3 on Apathy in AD Mouse Model

Abstract

Alzheimer's disease (AD) is characterized by a range of neurological and psychiatric symptoms, notably impacting learning and memory abilities. Currently, there is no treatment available that can prevent disease progression. As a global health concern, AD requires novel therapeutic approaches to reduce symptoms and prevent the disease from getting worse. The present work examines the possible synergistic effects of vitamin D3 (calcitriol) supplementation, either alone or in conjunction with donepezil, in reducing apathy and preventing progression. The AD mouse model was based on aluminum chloride (AlCl3)- induced neurotoxicity, with 64 mice split into treatment and control groups. Oral administration of AlCl3 (300 mg/kg) was followed by intraperitoneal injections of vitamin D3 (0.5 µg/kg) and donepezil (2 mg/kg) for a total of 15 days. A thorough battery of behavioral tests measured recognition memory, apathy, anxiety, and social behaviors through Elevated Plus Maze, Splash Test, Nest Building Test, Novel Object Recognition, and Social Novelty Preference. Histological examination was also performed to assess morphological damage induced by AlCl3. When compared to AlCl3-induced AD mice, the groups treated with vitamin D3, either alone or in conjunction with donepezil, showed significantly (p<0.0001) lower levels of anxiety-related behavior. Interestingly, the groups treated with vitamin D3 significantly (p<0.01) reduced apathy-like behaviors, which were reinforced by increased grooming and improved nest-building abilities. The vitamin D3-treated groups (p<0.01) and donepezil + vitamin D3-treated groups (p<0.001) significantly improved the recognition memory in the Novel Object Recognition test. The group treated with vitamin D3 + donepezil displayed significant improvement (p<0.05) in social behavior. Congo red staining revealed decreased Aβ aggregates in treated groups post administration of AlCl3. H & E staining of the brain tissues also indicated improved neuronal density in the treated groups. These findings showed that xi vitamin D3 has potential to reduce apathy and can enhance cognitive performance in neurodegenerative disorders. Combinational group outperform than the groups treated with donepezil and vitamin D3 alone, across all behavioral tests. The present results highlighted the potential of vitamin D3, either as a stand-alone or adjunctive treatment, in the management of AD and other neurodegenerative disorders pertaining apathy and anxiety like behavior. However further insight into the molecular mechanisms and synergistic effects of vitamin D3 are warranted for potential clinical use in the future.