Neuroprotective role of vitamin D3 in colchicine-induced Alzheimer’s disease in rats

Abstract

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disease characterized by progressive decline in memory, language and other cognitive functions. Recent studies provide convincing evidence on the role of vitamin D3 on the nervous system.
Aim: To investigate the effect of the active form of vitamin D3 (1,25-dihydroxycholecalciferol) as a neuroprotective agent in experimentally induced AD in rats.
Methods: 40 adult male Wistar (albino) rats weighing 180 to 200 g were included in this study. Rats were divided into four groups (each of 10 rats): Group I: normal healthy rats receiving intracerebroventricular injection (icv) of artificial cerebrospinal fluid (ACSF) and serving as a control group. Group II: rats with induced AD by icv colchicine injection of 15 lg/rat bilaterally and receiving no treatment. Group III: rats pre-treated with active form of vitamin D3 42 IU/kg/day subcutaneously (s.c.) for one week followed by induction of AD then post-treated with vitamin D3 in the same dose for 3 weeks. Group IV: rats with induced AD then post-treated with vitamin D3 for 3 weeks. The following parameters were evaluated in rats of all studied groups
1- Behavioral assessment: Morris water maze and open field tasks were performed at days   13, 14 and 21 post-icv injection for assessing cognitive, gross behavioral and motor activities of studied groups.
2- Biochemical tests: Hippocampal tissue levels of brain derived neurotrophic factor (BDNF), amyloid beta (Ab) peptide, and antioxidant system; glutathione reductase (GR) and glutathione peroxidase (GPX).
Results: The present study revealed a significant increase in time latency of water maze test and hippocampal tissue level of Ab peptide concomitant with significant reduction of hippocampal tissue levels of BDNF, GR and GPX, in untreated AD rats (group II) versus control ACSF-injected rats (group I) and vitamin D3-treated AD rats (groups III and IV). However, group III (AD rats pre- and post-treated with vitamin D3) showed a significant decrease in time latency and Ab peptide, and a significant elevation of BDNF, GR and GPX, versus group IV (AD rats post-treated with vitamin D3).
Conclusion: Prophylactic use of active form of vitamin D3 (1,25(OH)2D3) appears to possess a neuroprotective effect in AD involving various mechanisms. Hence, vitamin D3 or its analogues can be considered as promising agents for development of new prophylactic and therapeutic neuroprotectors.