Differential Effects of Sevoflurane Exposure on Long-Term Fear Memory in Neonatal and Adult Rats.

It remains unclear whether exposure to sevoflurane produces different effects on long-term cognitive function in developing and mature brains. In the present study, Sprague-Dawley neonatal rats at postnatal day (PND) 7 and adult rats (PND 56) were used in all experiments. We performed fear conditioning testing to examine long-term fear memory following 4-h sevoflurane exposure. We assessed hippocampal synapse ultrastructure with a transmission electron microscope. Moreover, we investigated the effect of sevoflurane exposure on the expression of postsynaptic protein 95 (PSD-95) and its binding protein kalirin-7 in the hippocampus. We observed that early exposure to sevoflurane in neonatal rats impairs hippocampus-dependent fear memory, reduces hippocampal synapse density, and dramatically decreases the expressions of PSD-95 and kalirin-7 in the hippocampus of the developing brain. However, sevoflurane exposure in adult rats has no effects on hippocampus-dependent fear memory and hippocampal synapse density, and the expressions of PSD-95 and kalirin-7 in the adult hippocampus are not significantly altered following sevoflurane treatment. Our results indicate that sevoflurane exposure produces differential effects on long-term fear memory in neonatal and adult rats and that PSD-95 signaling may be involved in the molecular mechanism for early sevoflurane exposure-caused long-term fear memory impairment.