Intense exercise can cause excessive apoptosis and synapse plasticity damage in rat hippocampus through Ca2+ overload and endoplasmic reticulum stress-induced apoptosis pathway
- Author:
- No author available
- Journal Title:
- Chinese Medical Journal
- Issue:
- 18
- DOI:
- 10.3760/cma.j.issn.0366-6999.20141191
- Key Word:
- intense exercise;exhaustion;hippocampus;endoplasmic reticulum stress-induced apoptosis;synapse plasticity;astrocytes activation
Abstract： Background Intense exercise can cause injury and apoptosis,but few studies have reported its effect on the central nervous system (CNS).The initial reason for hippocampus injury is the excitotoxicity of glutamate and calcium overload.Intracellular free Ca2+ ([Ca2+]i) overload may trigger the apoptosis pathway and neuron damage.The aim of this study was to investigate whether intense exercise could cause hippocampus apoptosis and neuron damage and then to determine which pathway was activated by this apoptosis.Methods We used one bout of swimming exhaustion rats as models.Intracellular [Ca2+]i was measured to estimate the calcium overload by Fura-2/AM immediately after exhaustion; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP)immunofluorescence were performed for estimating astrocyte activation and synapse plasticity 24 hours after exhaustion.Apoptosis cells were displayed using dUTP nick end labelling (TUNEL) stain; endoplasmic reticulum (ER) stress-induced apoptosis pathway and mitochondrial apoptosis pathway were synchronously detected by Western blotting.Results An increasing level of intracellular [Ca2+]i (P ＜0.01) was found in the hippocampus immediately after exhaustion.GFAP and SYP immunofluorescence showed that the astrocytes are activated,and the synapse plasticity collapsed significantly 24 hours after exhaustion.TUNEL stain showed that the number of apoptosis cells were notably raised (P ＜0.01); Western blotting of the apoptosis pathway showed increasing levels of caspase-3 cleavage (P ＜0.01),Bax (P ＜0.01),caspase-12 cleavage (P ＜0.01),C/EBP-homologous protein (CHOP) (P ＜0.01),and phospho-Junaminoterminal kinases (p-JNK; P ＜0.01) and decreasing level of Bcl-2 (P ＜0.01).Our results proved that exhaustion can induce hippocampus injury and apoptosis by [Ca2+]i overload,with collapsed synaptic plasticity as the injury pattern and ER stress-induced apoptosis as the activated pathway.Conclusion Intense exercise can cause excessive apoptosis and synapse plasticity damage in the hippocampus with [Ca2+]i overload as the initial reason,and thus provides leads for therapeutic interventions in the brain health of athletes.
- [1]Benedict C. Albensi.The NMDA Receptor/Ion Channel Complex: A Drug Target for Modulating Synaptic plasticity and Excitotoxicity[J].2007,13(31).
- [2]D P, Thomas,K I, Marshall.Effects of repeated exhaustive exercise on myocardial subcellular membrane structures.[J].1988,9(4).
- [3]Goda Y,Tarsa L.Synaptophysin regulates activity-dependent synapse formation in cultured hippocampal neurons.[J].2002,99(2).
- [4]Allen,S.,Fawer,J.L.,Kolobova,A.,etc.Exercise protects against chronic restraint stress-induced oxidative stress in the cortex and hippocampus[J].2013,1509.
- [5]Chen PE,Lipscombe D,Wyllie DJ,etc.Single-channel analysis of a point mutation of a conserved serine residue in the S2 ligand-binding domain of the NR2A NMDA receptor subunit.[J].2006,574(Pt.2).
- [6]Logue SE,Gorman AM,Samali A,etc.Mediators of endoplasmic reticulum stress-induced apoptosis[J].2006,7(9).
- [7]Teal S, Eich,Janet, Metcalfe.Effects of the stress of marathon running on implicit and explicit memory.[J].2009,16(3).
- [8]Bading H,Hardingham GE.The Yin and Yang of NMDA receptor signalling.[J].2003,26(2).
- [9]Farrant M,Brickley S,Cull-Candy S.NMDA receptor subunits: diversity, development and disease.[J].2001,11(3).
- [10]Ishibashi H.Increased synaptophysin expression through whisker stimulation in rat.[J].2002,22(2).
- [11]Sofroniew MV.Molecular dissection of reactive astrogliosis and glial scar formation.[J].2009,32(12).
- [12]Kumar S.Caspase function in programmed cell death.[J].2007,14(1).
- [13]Radha Aras,Anna M Barron,Christian J Pike.Caspase activation contributes to astrogliosis.[J].2012,1450.
- [14]Li YF,Huang WC,Yang M,etc.The cytoprotective effect of inulin-type hexasaccharide extracted from Morinda officinalis on PC12 cells against the lesion induced by corticosterone.[J].2004,75(13).
- [15]Wu,G.L.,Zhang,L.X.,Huang,X.D.,etc.Exhaustive swimming exercise related kidney injury in rats protective effects of acetylbritannilactone[J].2012,33(1).
- [16]Arias,J.L.,Sampedro-Piquero,P.,Begega,A.,etc.Effects of forced exercise on spatial memory and cytochrome c oxidase activity in aged rats[J].2013,1502.
- [17]Vieira FB,Cristina Rodrigues F,Oliveira da Silva A,etc.Increased apoptosis and reduced neuronal and glial densities in the hippocampus due to nicotine and ethanol exposure in adolescent mice.[J].2009,27(6).
- [18]E, Masliah,R D, Terry,R M, DeTeresa,etc.Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease.[J].1989,103(2).
- [19]TomásPereira,I.,Coletta,C.E.,Kim,D.H.,etc.CREB-binding protein levels in the rat hippocampus fail to predict chronological or cognitive aging[J].2013,34(3).
- [20]Hovda DA,Griesbach GS,Gomez Pinilla F.The upregulation of plasticity-related proteins following TBI is disrupted with acute voluntary exercise.[J].2004,1016(2).
- [21]Berliocchi L,Nicotera P,Bano D.Ca2+ signals and death programmes in neurons[J].2005,360(1464).
- [22]Kerr, A.L.,Swain, R.A..Rapid Cellular Genesis and Apoptosis: Effects of Exercise in the Adult Rat[J].2011,125(1).
- [23]Fernandes,J.,Baliego,L.G.Z.,Peixinho-Pena,L.F.,etc.Aerobic exercise attenuates inhibitory avoidance memory deficit induced by paradoxical sleep deprivation in rats[J].2013,1529.