Imperatorin restores behavioral and recognition memory deficits induced by REM sleep deprivation in male rats

Many studies have shown the deleterious effects of rapid-eye movement (REM) sleep deprivation (SD) on cognitive functions and synaptic plasticity markers. On the other hand, imperatorin (IMP, extracted from the fruits of Angelica dahurica and Peucedanum praeruptorum) may exert significant pro-cognitive and neuroprotective effects. The present study aimed to explore the potential therapeutic effects of IMP on behavioral and molecular changes induced by REM SD, before or after training in the novel object recognition (NOR) memory test. REM SD was done for 24 h and IMP was orally administered at the dose of 100 mg/kg (immediately after REM SD). Locomotion, anxiety-like behavior, and brain-derived neurotrophic factor (BDNF) and cAMP response element binding (CREB) levels were also assessed in the prefrontal cortex. The results showed that REM SD impaired NOR memory, reduced locomotor activity, increased anxiety- and depressive-like behaviors, with more severe effects of the post-train REM SD. Both pre- and post-train REM SD reduced BDNF and CREB mRNA expression levels in the prefrontal cortex. IMP could restore and increase BDNF and CREB expression levels, respectively, only in pre-train REM SD rats, and reduce behavioral impairments caused by pre- or post-train REM SD. In conclusion, imperatorin attenuated REM SD-induced recognition-memory and behavioral abnormalities, whereas its molecular effects were more selective and were limited to BDNF and CREB mRNA expression changes in the prefrontal cortex, particularly in the pre-train REM SD condition. These findings suggest that BDNF/CREB-related transcriptional modulation may contribute to, but may not fully explain, the behavioral effects of imperatorin.