β-Caryophyllene prevents cognitive impairment in mice following acute sleep deprivation by alleviating hippocampal structural and functional alterations

Sleep deprivation (SD) has become a prevalent issue leading to suboptimal health conditions. While, there is still a lack of effective intervention methods. Cannabinoid receptor type 2 (CB2R) is reported to possess anti-inflammatory properties and facilitate synaptic plasticity, while without the risk of causing psychological addiction. Here we administered β-caryophyllene (BCP), the highly selective CB2R agonist, and observed whether cognitive impairment following acute sleep deprivation (ASD) was prevented. Our results demonstrated that administration of BCP for 3 days before ASD markedly prevented both long-term spatial learning and memory, along with short-term episodic recall in mice exposed to ASD, but the four experimental groups of mice exhibited comparable hippocampal CB2R expression without marked differences. In addition, BCP effectively reversed the disruption of long-term potentiation (LTP) in the hippocampal CA1 area induced by ASD, but failed to reestablish long-term depression (LTD) or paired pulse ratio (PPR). Furthermore, BCP prevented synaptic ultrastructural alterations and promoted the recovery of both dendritic spine density and morphological complexity within the CA1 subfield of the hippocampus. Overall, these results indicate that BCP prevented cognitive impairment after ASD by preventing damage to synaptic function and structural plasticity, preventing alterations of pyramidal cell dendritic complexity and density of dendritic spines within CA1 subregion of hippocampi of mice. As a widely used dietary phytocannabinoid, BCP shows promise as a novel drug for preventing and treating cognitive impairment following ASD.