The spleen mediates chronic sleep restriction-mediated enhancement of LPS-induced neuroinflammation, cognitive deficits, and anxiety-like behavior

Abstract

Chronic sleep restriction promotes neuroinflammation and cognitive deficits in neurodegenerative and neurobehavioral diseases. The spleens of mice exposed to chronic and repeated psychological stress serve as a reservoir of inflammatory myeloid cells that are released into the blood and brain following secondary acute stress. Here, we tested whether chronic and repeated short-term sleep restriction (CRSR) would exacerbate lipopolysaccharide (LPS)-induced neuroinflammation, cognitive deficits, and anxiety-like behavior in a spleen-dependent manner. LPS was administered to aged mice 14 days after exposure to CRSR consisting of three cycles of 7 days of sleep restriction with 7-day intervals in between. CRSR increased plasma proinflammatory cytokine levels, blood-brain barrier permeability, hippocampal proinflammatory cytokine levels, and transition of microglia to the M1 phenotype 24 h after LPS treatment. This in turn led to cognitive deficits and anxiety-like behavior. Interestingly, removal of the spleen 14 days prior to CRSR abrogated the enhancement of LPS-induced increases in systemic inflammation, neuroinflammation, cognitive deficits, and anxiety-like behavior. These data indicate that the spleen was essential for CRSR-induced exacerbation of LPS-induced brain damage.

Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor

“…Depression-like behaviors, increased spleen volume, and abnormal composition of gut microbiota following injection of lipopolysaccharide (LPS) in mice were attenuated after subdiaphragmatic vagotomy, further suggesting a role of the brain–gut–microbiota axis via the vagus nerve [ 159 ]. Splenectomy prior to chronic sleep restriction abrogated the enhancement of LPS-induced increases in neuroinflammation and abnormal cognition and anxiety behaviors, implicating the spleen in sleep restriction-induced exacerbation of LPS-induced brain damage [ 160 ]. Moreover, stress-activated corticotropin-releasing hormone neurons control adaptive immunity in the spleen by direct innervation, suggesting a brain–spleen axis in the regulation of humoral immunity [ 161 , 162 ].…”

An investigation of foreign language writing anxiety and its reasons among pre-service EFL teachers in Pakistan

“…Avoidance behavior displays activities related to avoiding situations when someone has to write. Xu et al ( 2020 ) discovered cognitive anxiety to be the most severe, in contrast to Atay and Kurt ( 2006 ) in Turkey and Arindra and Ardi ( 2020 ) in Indonesia, whose participant's experienced somatic anxiety-associated with physiological arousal as their dominating form. It indicates that when completing a writing assignment, participants frequently worried excessively about what other people might think and had low standards for their writing (Cheng, 2004 ).…”

Night Shift Work Is Associated with Reduced Rate of Humoral Response Following Vaccination for HBV

“…Therefore, regular sleep promotes a correct immune response following antigenic stimulus since the immune system processes are organized according to circadian rhythms. Moreover, infections affect sleep regulation, most likely via proinflammatory cytokine production [ 1 ], and similarly, chronic sleep deprivation or sleep disruption increase the risk of severe chronic systemic diseases that have a low-grade inflammatory component, like diabetes, atherosclerosis, and neurodegeneration [ 2 ].…”