Early anesthetic exposure and long-term cognitive impairment.

Several lines of evidence from clinical cohort studies and animal studies have shown that early exposure to anesthetics is a significant risk factor for later development of learning disabilities. However, the underlying molecular mechanism is unclear. Recent studies have indicated that hippocampal neurogenesis and synaptogenesis may be involved in the mechanisms by which early anesthetic exposure produces long-term cognitive impairment. It is possible that synaptic scaffolding protein postsynaptic density-95 (PSD-95) PDZ (PSD 95/Discs large/Zona occludens-1) domain-mediated protein-protein interactions are involved in the regulation of neurogenesis and synaptogenesis in the central nervous system. PDZ domain-mediated protein-protein interactions are disrupted by clinically relevant concentrations of inhaled anesthetics. It will help us understand the molecular mechanism underlying anesthetic-induced long-term cognitive dysfunction if we can demonstrate the role of synaptic PDZ interactions in early anesthetic exposure-produced long-term cognitive impairment.