Geraniol (GER) attenuated chronic sleep restriction (CSR)-induced neuroinflammation in adolescent mice

Sleep insufficiency is a significant health problem worldwide, and adolescent sleep restriction (SR) could induce multiple neurodevelopmental disorders in the central nervous system (CNS). Microglial-mediated neuroinflammation plays a vital role in multiple neurological diseases, and recent research showed the regulation effect of immunoproteasome on microglia functions. Geraniol (GER), an important ingredient in many essential oils, possesses diverse pharmacological properties like anti-inflammatory and antioxidant. The present study was designed to evaluate the neuroprotective effect of GER on SR in adolescent mice and further investigate the underlying mechanisms. Our results displayed that 14 days of chronic sleep restriction (CSR) induced cognitive decline, and anxiety-like and attention-deficit behaviors, which were mitigated by GER pretreatment. GER administration also reversed microglial pro-inflammatory response under CSR stimulation in the anterior cingulate cortex (ACC) regions by reducing the expression and secretion of cytokines like IL-1β and TNF-α. Mechanism research showed that LMP7 mRNA was selectively up-regulated under CSR treatment but down-regulated by GER administration. Proteasome activity and protein expression of LMP7 were consistent with mRNA data. ONX-0914 was applied to inhibit LMP7 selectively, and data validated that GER might alleviate CSR-induced neuroinflammation by regulating LMP7. Our study provides evidence that LMP7 is a critical regulator of CSR-induced proinflammation, and geraniol might be a promising therapy against CSR-induced neurodevelopmental disorders.