Amelioration of cognitive and biochemical impairment in Aβ-based rodent model of Alzheimer's disease following fractionated X-irradiation.

Alzheimer's disease is characterized by deposition of amyloid-beta plaques in the brain. Available pharmaceuticals provide temporary symptomatic relief without affecting disease progression. Use of radiation was found effective in treating extra-cranial amyloidosis, therefore, the present study was designed to investigate the neuroprotective role of fractionated X-irradiation in Aβ 1-42 -based rodent model of Alzheimer's disease. S.D. female rats were randomly divided into four groups: sham control (Group 1), Aβ 1-42 injected (Group 2), cranial X-irradiated (Group 3) and Aβ 1-42 injected followed by cranial X-irradiation (Group 4). A single dose of 5 µL Aβ 1-42 peptide was administered through intracerebroventricular (icv) injection in Group 2 and 4 animals, while Group 1 animals were administered 5 µL of bi-distilled water (icv). The group 4 animals were further subjected to 10 Gy X-irradiation (fractionated dose, 2 Gy × 5 days) after 4 weeks of Aβ 1-42 infusion of peptide. The animals in Group 3 were subjected to same dose of cranial fractionated X-irradiation (2 Gy × 5 days) only. Significant decrease in amyloid deposits were observed in the Aβ 1-42  + radiation-treated animals confirmed by histopathological analysis. These finding were in concordance with neurobehavioral tests that showed a significant improvement in Aβ 1-42 -induced memory impairment in the animals subjected to fractionated cranial X-irradiation. Restoration of alterations in neurochemical and antioxidant defense indices further supported our results. The present study highlights the underexplored role of fractionated X-irradiation in curtailing the Aβ 1-42 -induced neurotoxicity, suggesting a novel treatment option for Alzheimer's disease-associated pathologies.