Oxidative stress mediated neuroinflammation induced by chronic sleep restriction as triggers for Alzheimer’s disease

• Published in: Alzheimer's & dementia Vol. 18; no. S3
• Main Authors: R.P., Parameswari, Ramesh, Girish, Chidambaram, Saravana Babu, Thangavelu, Lakshmi
• Format: Journal Article
• Language: English
• Published: 01.12.2022
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.059016

Background Overactivation of brain renin angiotensin system (RAS) has shown to be associated with initiation and progression of Alzheimer’s disease (AD) through increased production of amyloid beta and oxidative stress resulting in cognitive impairment. Further, chronic sleep restriction (CSR) also shown to induce increased production of amyloid beta. Angiotensin converting enzyme inhibitors has been stated to possess beneficial effect against AD. However, the mechanisms still needs to be studied. In the present study we have investigated the effect of CSR on memory and biological functions in mice for better understanding of its effect in initiating AD and also the protective effect of ACEI, Captopril Materials and Methods Chronic sleep restriction was induced in C57BL/6J mice for 18 h continuously, with intermittent recovery for 6h using multiple platform method for 21 days. Captopril 20mg/kg b.wt. was administered for 21 days, 30 mins before subjecting the animals to CSR. Memory functions were assessed by novel object recognition test and radial arm maze. Oxidative stress markers and antioxidant enzymes were determined in the hippocampus. Protein levels of Aβ and tau protein and inflammatory markers in the hippocampus was done by immunoblot and ELISA. The ultrastructure of the hippocampus was observed. Key Results Mice chronically restricted of sleep demonstrated significant impairment in the memory function which was found to be significantly improved by captopril pre‐treatment. Further, CSR mice showed elevated level of oxidative stress marker, LPO with concomitant decrease in antioxidants viz., SOD, and GSH which was also restored by captopril. Captopril pre‐treatment has markedly reduced Aβ and tau protein levels with concomitant decrease in the levels of inflammatory markers. The ultrastructure of CSR mice showed shrunken nuclear membrane with abnormal mitochondria in CSR mice which was moderately restored by Captopril. Conclusion The present study showed impaired memory functions with increased incidence of oxidative stress in CSR mice which might act as a trigger for neuroinflammation. The present study data support the implication of oxidative stress and neuroinflammation in the onset and progression of Alzheimer’s disease. Further, the results of the present study also showed that captopril exert protective effect against Alzheimer’s disease by attenuating oxidative stress.