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Updated: May 6, 2026
A Lateralized Odor Learning Model in Neonatal Rats for Dissecting Neural Circuitry Underpinning Memory Formation
Published on: August 18, 2014
Role of NMDAR-NMNAT in sevoflurane exposure-induced learning memory deficits
Nan Hu1, Weiwei Ji2, Jing Dou1
1Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Tianjin 300060, China.
Objective:
This study investigated the roles of CREB and NMNATs in sevoflurane-induced cognitive deficits and synaptic alterations in developing hippocampal neurons.
Methods:
160 postnatal day-7 male SD rats were randomized into four groups: Control; Sevo (3% sevoflurane for 6 h); Sevo+D-cycloserine (DCS, an NMDA receptor agonist); and AP-5 (an NMDA receptor antagonist). Cognitive function was assessed at 8 weeks using the Morris water maze. Dendritic spine density/morphology in hippocampal CA1 was analyzed via Golgi-Cox Staining. Protein levels of NMNAT1, NMNAT2, CREB, and p-CREB were measured by western blot and immunofluorescence.
Results:
Compared to controls, sevo-exposed rats exhibited significant spatial memory impairment, demonstrated by increased escape latency, longer path length, and fewer platform crossings. This group also showed reduced dendritic spine density and altered morphology in CA1, alongside decreased p-CREB and NMNAT1/2 expression. In contrast, DCS pretreatment before sevo exposure reversed these deficits, restoring cognitive performance, spine density/morphology, and p-CREB/NMNAT1/2 levels.
Conclusion:
Sevoflurane induces learning/memory deficits and dendritic spine pathology in neonatal rats, likely via NMDA receptor-mediated downregulation of p-CREB and NMNAT1/2. DCS pretreatment effectively mitigates these effects, highlighting that enhancing NMDA receptor activity can counteract sevoflurane-induced neurotoxicity. NMDA receptor modulation represents a promising therapeutic strategy for postoperative cognitive dysfunction.
