ROLE OF RADIATION AS EFFECTIVE INTERVENTION IN Aβ INDUCED OXIDATIVE STRESS IN ANIMAL MODEL OF ALZHEIMER'S DISEASE

Abstract

Objective: The present study was undertaken to study the therapeutic effects of low dose fractionated cranial X-irradiation on reducing the amyloid-beta (Aβ) induced oxidative stress burden in an animal model of Alzheimer's disease (AD).

Methods: S.D. female rats received an intracerebroventricular injection of Aβ peptide at stereotaxically defined points. Experimental sessions were conducted by randomly dividing animals into four groups, namely sham-operated, Aβ-injected, and Aβ injection followed by cranial X-irradiation and only cranial X-irradiated. Anesthetized animals received 5 μl synthetic Aβ peptide injection with a 10 μl Hamilton microsyringe with the needle kept in place for a period of 2min following injection. Sham-operated group received 5 μl of bidistilled water instead of Aβ peptide. Animals were treated 6 weeks post-surgery with fractionated radiation of 2Gy for 5 days. Neurobehavior studies were undertaken to confirm memory impairment along with biochemical indices involved in the antioxidant defense system.

Results: Fractionated cranial X-irradiation proved effective in restoration of activity of enzymes involved in the antioxidant defense system; the lipid peroxidation and catalase levels that showed a significant increase in Aβ-treated group decreased on subsequent X-irradiation. Moreover, the decrease in the superoxide dismutase, glutathione, glutathione-S-transferase, and glutathione reductase levels witnessed an increase post-irradiation, implicating the X-irradiation to be an effective intervention to restore the redox status of the oxidatively stressed brain cells in AD condition.

Conclusion: The present study evaluated the therapeutic potential of low dose fractionated cranial X- irradiation by mitigating the amyloid-induced oxidative stress suggesting a novel treatment for AD-associated pathologies.