PD201 - NEUROPROTECTIVE ACTIONS OF VITAMIN D3 IN CHRONIC UNPREDICTABLE MILD STRESS-EXPOSED RATS: INVOLVEMENT OF HIPPOCAMPAL WNT/Β-CATENIN PATHWAY

Linked sessions

PD201

NEUROPROTECTIVE ACTIONS OF VITAMIN D3 IN CHRONIC UNPREDICTABLE MILD STRESS-EXPOSED RATS: INVOLVEMENT OF HIPPOCAMPAL WNT/Β-CATENIN PATHWAY

M. M. Alrashed1, H. Tabassum1, D. Aldisi2,*, M. H. Alhussain3, S. Arjumand1, M. M. A. Abulmeaty2

1Clinical Laboratory Sciences, 2Community Health Sciences, 3Food Science and Nutrition, King Saud University, Riyadh, Saudi Arabia

 

Rationale: Neurobiological disturbances during Chronic Unpredictable Mild Stress (CUMS) impair neuronal integrity, plasticity, and cognitive performance. The Wnt/β-catenin (WβC) pathway is a potential neuroprotective mechanism that mitigates oxidative stress, inflammation. The neuromodulatory properties of Vitamin D3 in CUMS-exposed rats may modulate this pathway. This study examined whether vitamin D3 ameliorates CUMS-induced alterations in Wnt/β-catenin signaling pathway in the hippocampaus.

Methods: Thirty-two rats were assigned to four groups: Control, CUMS only, CUMS + vitamin D3 (1000 IU/kg), and CUMS + vitamin D3 (10,000 IU/kg). CUMS rat model was produced by exposing rats to unpredictable doses of social and physical stressors according to our previous work1. Vitamin D3 was administered intramuscularly three times weekly for 4 weeks. Hippocampal mRNA expression of Wnt pathway components and BDNF was quantified by RT-qPCR using the 2−ΔΔCt method.

Results: CUMS markedly disrupted canonical Wnt/β-catenin signaling, evidenced by significant downregulation of Wnt1, β-catenin, and Axin2 mRNA expression (all p < 0.05), together with a robust upregulation of GSK-3β mRNA (p < 0.001) (Figure 1). This transcriptional imbalance was accompanied by reduced BDNF mRNA expression (p < 0.05). Vitamin D3 supplementation effectively counteracted these transcriptional and biochemical disturbances, restoring β-catenin stability and enhancing downstream gene expression.

Image:



 

Conclusion: These findings indicate that vitamin D3 exerts significant neuroprotective effects in CUMS rat models by modulating Wnt/β-catenin signaling as a mechnism of action.

References: Al-Ramadhan FR, Abulmeaty MMA, Alquraishi M, Razak S, Alhussain MH. Effect of Vitamin D3 on Depressive Behaviors of Rats Exposed to Chronic Unpredictable Mild Stress. Biomedicines. 2023; 11(8):2112.

Disclosure of Interest: None declared