Age-Related Alteration Of NSF Levels In Different Brain Regions And Their Correlations With Spatial Learning Memory In Mice

Background Numerous studies have demonstrated that learning and memory functions are impaired with aging from rodents to human. However, the underlying mechanism leading to this cognitive decline is still incompletely clear. Nowadays, it is thought that the destruction of synaptic integrity may result the age-related cognitive decline. N-ethylmaleimide-sensitive fusion protein (NSF), one kind of ATPase, is considered one of the important proteins in the process of synaptic transmission, which also played an important role in the process of membrane fusion between the synaptic vesicles and presynaptic neurotransmitter release. Several studies showd that in animal models with learning memory impairment, the expression of NSF decreased in the hippocampus, which suggests that NSF may affect the normal neurotransmitter release and LTP formation, then leads to learning and memory dyfunction. However, NSF in the normal aging process and its trend in spatial cognitive function remain unknown.Objectiveâ‘ To explore the effects of aging on the levels of NSF in different brain regions;â‘¡To explore the correlation between the levels of NSF in these brain regions and spatial learning memory ability.Methods Three ages of Kunming (22, 11 and 6 months) and SAMP8 mice (13, 9 and 5 months) were selected, which have been tested by six-arm radial water maze (RAMW). The expressions of NSF and GAPDH (reference protein) in dorsal hippocampus, ventral hippocampus, frontal lobe, parietal lobe and olfactory bulb were detected by Western blot. The ratio of the NSF-GAPDH in gray-scale value was regarded as the relative content of the NSF. One-way ANOVA was used to analyze the effect of the age on the relative content of NSF. And the Spearman correlation test was used to analyze the correlation between the relative amount of NSF protein and the average latency and number of errors of cognitive task.Resultsâ‘ For Kunming mice, the relative NSF amount in the dorsal hippocampus of the mice aged 11 and 22 months was significantly higher than that in the 6-month-old mice (Ps < 0.05), but there was no significant difference between 11-month-old mice and 22-month-old mice (P > 0.05). There were also no significantly age-related changes of the relative content of NSF in the ventral hippocampus, frontal, parietal, and olfactory bulb (Ps > 0.05).â‘¡For SAMP8 mice, the relative amount of the NSF in the dorsal hippocampus, frontal lobe and parietal lobe of the 13-month-old mice was significantly higher than those in the 5-month-old mice (Ps < 0.05), and the amount of the NSF in the 13-month-old mice in the dorsal hippocampus was also higher than that in the 9-month-old mice (P < 0.05). The relative content of NSF in the ventral hippocampus and olfactory bulb was observed unsignificance (Ps > 0.05).â‘¢For Kunming and SAMP8 mice,significantly positive correlations were observed between the relative amount of the NSF in the dorsal hippocampus and the average latency and number of errors during learning and memory phases (Ps < 0.05).Conclusionâ‘ In Kunming and SAMP8 mice, the amount of NSF in the dorsal hippocampus significantly increased with aging.â‘¡Increased NSF in the dorsal hippocampus may be involved in the age-related spatial cognitive impairment.