The ameliorative effect of fluoxetine on neuroinflammation induced by sleep deprivation

Abstract It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation ( SD ) can trigger neuroinflammation in the brain. The nucleotide‐binding domain and leucine‐rich repeat protein‐3 ( NLRP 3) inflammasome is reported to be relevant to the neuroinflammation induced by SD , but the regulatory signaling that governs the NLRP 3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure. In this study, we were the first to discover that the antidepressant fluoxetine, a type of specific serotonin reuptake inhibitor widely used in clinical practice, could suppress the neuroinflammation and neuronal apoptosis induced by SD . The main findings from this study are as follows: (i) SD stimulated the expression of activated NLRP 3 inflammasomes and the maturation of IL ‐1β/18 via suppressing the phosphorylation of STAT 3 in astrocytes; (ii) SD decreased the activation of AKT and stimulated the phosphorylation of GSK ‐3β, which inhibited the phosphorylation of STAT 3; (iii) the NLRP 3 inflammasome expression stimulated by SD was partly mediated by the P2X7 receptor; (iv) an agonist of STAT 3 could significantly abolish the expression of NLRP 3 inflammasomes induced by an agonist of the P2X7 receptor in primary cultured astrocytes; (v) the administration of fluoxetine could reverse the stimulation of NLRP 3 inflammasome expression and function by SD through elevating the activation of STAT 3. In conclusion, our present research suggests the promising possibility that fluoxetine could ameliorate the neuronal impairment induced by SD . image