Abstract
The upstream signal molecule modulating neuro-inflammation and synaptic changes during the pathogenesis of postoperative cognitive dysfunction (POCD) is still elusive. Here, we examined the effects and mechanisms of energy sensor AMP-activated protein kinase (AMPK) in the pathogenesis of POCD. Our data showed that surgery significantly increased the expression of p-AMPK in aged rats (p < 0.05), but not in adult rats (p > 0.05). Moreover, inhibiting AMPK activation via compound C during operation significantly improved surgery-induced impairment of the learning and memory of aged rats in water maze (p < 0.05). Further mechanism studies showed that corresponding to the impairment of learning and memory after surgery, surgery significantly increased the activation of microglia, decreased the expressions of NR2B and p-NR2B, and increased the expressions of Tau and p-Tau, which also were obviously restored by inhibiting AMPK during operation. In contrast, Inhibiting AMPK activation during operation didn't change ATP level in the hippocampus of aged rats after surgery. These data suggest that surgery induced activation of AMPK in hippocampus in an age-dependent manner. AMPK plays important roles in POCD of aged rats via multiple mechanisms, and is a possible molecular target for the prevention and treatment of POCD.