Sepsis-associated encephalopathy (SAE) is associated with a higher risk of cognitive deficits; however, its potential mechanisms are still unknow. Recently, researches show that HSPB8, a family of small heat shock proteins, affects cognitive function and ameliorates sepsis-induced dysfunction. However, the role of HSPB8 in SAE-associated cognitive impairment has not been elucidated. In this study, we found that HSPB8 expression was up-regulated in the brain of mice with lipopolysaccharide-induced sepsis. HSPB8 overexpression alleviated cognitive decline in SAE mice. In addition, exogenous HSPB8 exerts neuroprotective effects and salvages synaptic function via regulating NRF1/TFAM-induced mitochondrial biogenesis and DRP1-mediate mitochondrial fission in a lipopolysaccharide-induced mouse model. Furthermore, HSPB8 overexpression inhibits IBA1 and NLRP3 activation in the SAE model. Overexpression of HSPB8 may be an efficient treatment for relieving SAE-related cognitive decline.
Keywords: Cognitive impairment; HSPB8; Mitochondria; Sepsis-associated encephalopathy.
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