Prophylactic Melatonin Treatment Ameliorated Propofol-Induced Cognitive Dysfunction in Aged Rats

Considering the fact that melatonin acts as protective agent in various cognitive impairment, we decided to explore the precise effect of pretreatment with melatonin on cognitive function, mitochondrial activity, apoptosis and synaptic integrity in aged rats anesthetized by propofol. We first randomly allocated the thirty Sprague Dawley rats into three groups: Control vehicle-treated group (Con), Propofol-treated group (Pro) and Melatonin + Propofol group (Mel + Pro). The Barnes maze, open field and contextual fear conditioning test were employed to evaluate spatial memory, exploratory behavior and general locomotor activity, and hippocampus-dependent learning and memory ability, respectively. Moreover, mitochondrial function (including reactive oxygen species, mitochondrial membrane potential and ATP levels) and apoptosis were detected in the regions of hippocampus (HIP) and prefrontal cortex (PFC). The results of behavioral tests suggested that melatonin improved propofol-induced memory impairment in aged rats. Melatonin mitigated mitochondrial dysfunction and decreased the apoptotic cell counts in the regions of HIP and PFC. Furthermore, prophylactic melatonin treatment also reversed the propofol-induced inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction. On the whole, our results indicated that melatonin ameliorated the propofol-induced cognitive disorders via attenuating mitochondrial dysfunction, apoptosis, inactivation of PKA/CREB/BDNF signaling and synaptic dysfunction.