Molecular mechanism of action of small molecule peptide-SMT(S)for ameliorating insomnia based upon PI3K/Akt signaling pathway
OBJECTIVE To explore the mechanism of action of SMT(S)in ameliorating insomnia and insomnia-induced secondary cognitive impairment,anxiety and immunodeficiency in mice.METHODS Para-chlorophenylalanine(PCPA)was applied for establishing an animal model of insomniac mice.Sedative-hypnotic effect of SMT(S)as well as improvement of anxi-ety and capability of learning and memory were explored through behavioral experiments and detecting neurotransmitter contents in sera.Capability of enhancing immune function was detected by NK cell killing and T-lymphocyte transformation assays and West-em blot was applied for detecting the protein expressions of PI3K/Akt signaling pathway.RESULTS SMT(S)reduced resi-dence time,distance traveled and average speed of insomniac mice in central compartment of open field and shortened the latency to disembarkation and total distance traveled in water maze;boosted the serum level of 5-HT as well as lowered the levels of DA and NE;elevated the rate of NK-cell killing and index of lymphocyte stimulation;and up-regulated the expressions of PI3K,Akt and mTOR proteins in brain tissues of insomniac mice.CONCLUSION SMT(S)may effectively prevent insomnia,signifi-cantly improve learning/memory capability and anxiety and enhance immune function in insomniac mice.Its molecular mechanism is correlated with the regulation of PI3K/Akt signaling pathway.Thus SMT(S)treats insomnia and insomnia-induced secondary cognitive impairment,anxiety and immuno compromise through regulating the signaling pathway of PI3K/Akt.
NETL
NSTL
万方数据
