不同强度训练负荷对大鼠认知情绪变化及NMDA受体、PSD-95和KIF-17mRNA和蛋白表达的影响
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摘要
目的:建立SD大鼠中等和高强度持续训练运动模型,探究不同训练负荷下,大鼠海马N-甲基-D-天冬氨酸受体(NMDARs)、突触后致密物质-95(PSD-95)和驱动蛋白家族蛋白17(KIF-17)表达及认知和情绪功能的变化。方法:实验建立SD大鼠跑台运动模型,分别进行中等和高强度持续训练4周,中等强度运动时采用递增负荷训练,高强度运动时采用高速训练,并设立正常对照组。测量运动后大鼠体质量减轻程度的变化,real-time PCR和Western blotting分别检测不同训练负荷对大鼠海马NMDA受体,PSD-95和KIF-17 m RNA和蛋白表达的影响。结果:相比对照组,中等强度持续运动精神状态明显更佳,高强度持续运动状态萎靡。中等强度持续训练组PSD-95、KIF-17和NMDA受体的m RNA和蛋白的表达显著上升(P<0.05),而高强度持续训练组m RNA和蛋白的表达则受到抑制(P<0.05)。结论:不同训练负荷对大鼠认知情绪及精神状态有较大影响,可以影响大鼠NMDA受体、PSD-95和KIF-17 m RNA和蛋白的表达。适量的运动训练不仅可以减轻缺氧对海马的损害,更可以有效地改善海马的功能。
Objective: To explore the changes of cognitive and emotional functions as well as the m RNA and protein expressions of N- methyl- D- aspartate receptors(NMDARs), postsynaptic density 95(PSD- 95) and kinesin family member 17(KIF-17) in hippocampus for long-term moderate-intensity and high-intensity training models in rats.Method: The exercise model of SD rats were established by treadmill running of moderate or high intensity for 4 weeks. The rats in the moderate intensity group were given endurance training with incremental intensity,while the high- speed training in the high intensity group. And we also set the normal control group. The body weight of rats was measured before and after exercise in order to determine the reduction. Real- time PCR and Western blotting were used to detect the m RNA and protein expressions of NMDARs, PSD- 95 and KIF-17 in hippocampus under different training loads.Result: Compared with those in the control group, the rats in the moderate-intensity group had better mental status, while a dispirited mental status in the high-intensity group. In the moderate-intensity group, the m RNA and protein expressions of PSD-95, KIF-17 and NMDARs were significantly increased(P<0.05) with the sup-pressed expressions in the high-intensity group(P<0.05).Conclusion: Different training loads have great influences on the cognition, emotion and mental status of rats,and can affect the m RNA and protein expressions of NMDARs, PSD-95 and KIF-17. Appropriate training can not only alleviate the damage of hypoxia to hippocampus, but also effectively improve the function of hippocampus.
Objective: To explore the changes of cognitive and emotional functions as well as the m RNA and protein expressions of N- methyl- D- aspartate receptors(NMDARs), postsynaptic density 95(PSD- 95) and kinesin family member 17(KIF-17) in hippocampus for long-term moderate-intensity and high-intensity training models in rats.Method: The exercise model of SD rats were established by treadmill running of moderate or high intensity for 4 weeks. The rats in the moderate intensity group were given endurance training with incremental intensity,while the high- speed training in the high intensity group. And we also set the normal control group. The body weight of rats was measured before and after exercise in order to determine the reduction. Real- time PCR and Western blotting were used to detect the m RNA and protein expressions of NMDARs, PSD- 95 and KIF-17 in hippocampus under different training loads.Result: Compared with those in the control group, the rats in the moderate-intensity group had better mental status, while a dispirited mental status in the high-intensity group. In the moderate-intensity group, the m RNA and protein expressions of PSD-95, KIF-17 and NMDARs were significantly increased(P<0.05) with the sup-pressed expressions in the high-intensity group(P<0.05).Conclusion: Different training loads have great influences on the cognition, emotion and mental status of rats,and can affect the m RNA and protein expressions of NMDARs, PSD-95 and KIF-17. Appropriate training can not only alleviate the damage of hypoxia to hippocampus, but also effectively improve the function of hippocampus.
引文
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[21]Shin MK,Jung WR,Kim HG,et al.The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway[J].Neuropharmacology,2014,77(2):414—421.
[2]Aguiar AS Jr,Castro AA,Moreira EL,et al.Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats:involvement of hippocampal plasticity via AKT,CREB and BDNF signaling[J].Mechan Ageing Dev,2011,132(11):560—567.
[3]Xuan A,Long D,Li J,et al.Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in beta-amyloid rat model of Alzheimer's disease[J].J Neuroinflammation,2012,9(1):202.
[4]Burnashev N,Szepetowski P.NMDA receptor subunit mutations in neurodevelopmental disorders[J].Curr Opin Pharmacol,2015,20:73—82.
[5]Levine BD.VO2max:what do we know,and what do we still need to know?[J].J Physiol,2008,586(1):25—34.
[6]Wolf OT,Bauser DS,Daum I.Eyeblink conditional discrimination learning in healthy young men is impaired after stress exposure[J].Psychophysiology,2012,49(2):164—171.
[7]Henneberger C,Bard L,King C,et al.NMDA receptor activation:two targets for two co-agonists[J].Neurochem Res,2013,38(6):1156—1162.
[8]Tanaka K.Brain development and glutamate[J].Brain Nerve,2013,65(10):1121—1132.
[9]Brigman JL,Wright T,Talani G,et al.Loss of Glu N2B-containing NMDA receptors in CA1 hippocampus and cortex impairs Long-Term Depression,reduces dendritic spine density,and disrupts learning[J].J Neurosci,2010,30(13):4590—4600.
[10]Robles JC,Sturek M,Parker JL,et al.Ca2+sensitization and PKC contribute to exercise training-enhanced contractility in porcine collateral-dependent coronary arteries[J].Am J Physiol Heart Circ Physiol,2011,300(4):H1201—H1209.
[11]Marmol F,Sanchez J,Lopez D,et al.Role of oxidative stress and adenosine nucleotides in the liver of aging rats[J].Physiol Res,2010,59(4):553—560.
[12]Hardingham GE.Coupling of the NMDA receptor to neuroprotective and neurodestructive events[J].Biochem Soc Trans,2009,37(Pt 6):1147.
[13]Miller LE,Mc Ginnis GR,Kliszczewicz B,et al.Blood oxidative-stress markers during a high-altitude trek[J].Int J Sport Nutr Exerc Metab,2013,23(1):65—72.
[14]Delint-Ramírez I,Salcedo-Tello P,Bermudez-Rattoni F.Spatial memory formation induces recruitment of NMDA receptor and PSD-95 to synaptic lipid rafts[J].J Neurochem,2008,106(4):1658—1668.
[15]Yin X,Takei Y,Kido MA,et al.Molecular motor KIF17is fundamental for memory and learning via differential support of synaptic NR2A/2B levels[J].Neuron,2011,70(2):310—325.
[16]Hardingham GE,Bading H.Synaptic versus extrasynaptic NMDA receptor signalling:implications for neurodegenerative disorders[J].Nat Rev Neurosci,2010,11(10):682—696.
[17]Kaut O,Schmitt I,Hofmann A,et al.Aberrant NMDA receptor DNA methylation detected by epigenome-wide analysis of hippocampus and prefrontal cortex in major depression[J].Eur Arch Psychiatry Clin Neurosci,2015,265(4):331—341.
[18]Burnouf S,Martire A,Derisbourg M,et al.NMDA receptor dysfunction contributes to impaired brain-derived neurotrophic factor-induced facilitation of hippocampal synaptic transmission in a Tau transgenic model[J].Aging Cell,2013,12(1):11—23.
[19]Müller L,Tokay T,Porath K,et al.Enhanced NMDA receptor-dependent LTP in the epileptic CA1 area via upregulation of NR2B[J].Neurobiol Dis,2013,54:183—193.
[20]Shipton OA,Paulsen O.Glu N2A and Glu N2B subunit-containing NMDA receptors in hippocampal plasticity[J].Philos Trans R Soc Lond B Biol Sci,2014,369(1633):20130163—20130163.
[21]Shin MK,Jung WR,Kim HG,et al.The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway[J].Neuropharmacology,2014,77(2):414—421.