1. Minocycline inhibits sleep deprivation-induced aberrant microglial activation and Keap1-Nrf2 expression in mouse hippocampus.
- Author
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Ahmed, Adeel, Misrani, Afzal, Tabassum, Sidra, Yang, Li, and Long, Cheng
- Subjects
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MICROGLIA , *FRACTALKINE , *HIPPOCAMPUS (Brain) , *MINOCYCLINE , *THETA rhythm , *ANXIETY , *SLEEP deprivation , *SUCROSE - Abstract
• SD causes microglial activation and Keap1-Nrf2 reduction in the mouse hippocampus. • SD alters theta, beta, and high gamma oscillations in the mouse hippocampus. • SD induces anxiety-like and depressive-like behavior in mice. • Minocycline inhibits microglial activation and Keap1-Nrf2 reduction in SD mice. • Minocycline normalizes brain oscillations and behavioral alteration in SD mice. Sleep deprivation (SD) is a hallmark of modern society and associated with many neuropsychiatric disorders, including depression and anxiety. However, the cellular and molecular mechanisms underlying SD-associated depression and anxiety remain elusive. Does the neuroinflammation play a role in mediating the effects of SD? In this study, we investigated SD-induced cellular and molecular alterations in the hippocampus and asked whether treatment with an anti-inflammatory drug, minocycline, could attenuate these alterations. We found that SD animals exhibit activated microglia and decreased levels of Keap1 and Nrf2 (antioxidant and anti-inflammatory factors) in the hippocampus. In vivo local field potential recordings show decreased theta and beta oscillations, but increased high gamma oscillations, as a result of SD. Behavioral analysis revealed increased immobility time in the forced swim and tail suspension tests, and decreased sucrose intake in SD mice, all indicative of depressive-like behavior. Moreover, open field test and elevated plus maze test results indicated that SD increases anxiety-like behavior. Interestingly, treatment with the microglial modulator minocycline prevented SD-induced microglial activation, restored Keap1 and Nrf2 levels, normalized neuronal oscillations, and alleviated depressive-like and anxiety-like behavior. The present study reveals that microglial activation and Keap1-Nrf2 signaling play a crucial role in SD-induced behavioral alteration, and that minocycline treatment has a protective effect on these alterations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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