Protective Effect Of Carnosine Against MDA-induced Impairment Of Hippocampal LTP In Rat

MDA (malondialdehyde) is a deleterious end-product in the process of ROS (reactive oxygen species)-induced lipid peroxidation. It's a bio-toxic unsaturated aldehyde. Effects of ROS in LTP are concerned in recent years, but the mechanism about how ROS results in those effects are not well understood. Carnosine is considered as a natural antioxidant. Recent studies have shown that carnosine could act as a natural scavenger of unsaturated aldehydes.Field potential, western blotting and calcium imaging were used to study MDA-induced impairment of hippocampal LTP in rat and the protective effect of carnosine against the impairment.PartⅠProtective effect of carnosine against MDA-induced impairment of hippocampal LTP in ratBackground: To investigat the effects of MDA on hippocampal LTP and the protective effect of carnosine against MDA-induced LTP impairment.Methods: Field potential recording in vivo.Results: Intracerebroventricular (icv) administration of MDA did not affect the basal amplitude of dentate gyrus field potential, but impaired the expression of LTP following application of HFS in a dose-dependent manner. The average of PS amplitudes 50–60 min after HFS were reduced to 182.0±6.4%, 179.0±6.3%, 147.7±7.1% (p<0.05 vs control), 128.0±6.8% (p<0.01 vs control) from 182.1±5.1% (control) when treated with 0.1, 1, 10, 100 mM MDA, respectively. Icv administration of carnosine did not affect the expression of LTP. The average of PS amplitudes 50–60 min after HFS was 182.0±6.8%. However, pretreatment with carnosine (200 mM) inhibited MDA-induced impairment of LTP. The average of PS amplitudes 50–60 min after HFS were increased to 178.9±6.6% (p<0.05 vs MDA alone), 133.6±5.5% when treated with 10, 100 mM MDA, respectively. Conclusions: MDA impaired the hippocampal LTP in a dose-dependent manner. Carnosine could inhibit the MDA-induced impairment of LTP, but it did not affect LTP when used alone.PartⅡThe protective mechanisms of carnosine against MDA-induced hippocampal LTP impairmentBackground: To study the mechanisms of MDA-induced impairment of hippocampal LTP and the protective effect of carnosine against the impairment.Methods: Western blotting and calcium imaging.Results: Calcium imaging showed that MDA stimulated [Ca2+]i increase in a dose-dependent manner. [Ca2+]i increased by 21.4±4.3%, 44.5±3.6%, 58.0±7.5% when treated 0.05, 0.1, 1 mM MDA, respectively. Western blotting showed that there was no significant change in CaMKⅡlevel in MDA-treated group. But, p-CaMKⅡlevel was significantly decreased. Pretreatment with carnosine did not affect CaMKⅡlevel but inhibited MDA-induced decrease of p-CaMKⅡlevel .Conclusion: MDA elevated [Ca2+]i in cultured hippocampal neurons in a dose-dependent manner. The effect of MDA on LTP induction was related to the inhibitory effect on CaMKⅡactivity. Carnosine antagonized MDA-induced inhibitory effect on CaMKⅡactivity.