Physical exercise improves synaptic dysfunction and recovers the loss of survival factors in 3xTg-AD mouse brain.
Physical exercise has become a potentially beneficial therapy for reducing neurodegeneration symptoms in Alzheimer's disease. Previous studies have shown that cognitive deterioration, anxiety and the startle response observed in 7-month-old 3xTg-AD mice were ameliorated after 6 months of free access to a running wheel. Also, alterations in synaptic response to paired-pulse stimulation were improved. The present study further investigated some molecular mechanisms underlying the beneficial effects of 6 months of voluntary exercise on synaptic plasticity in 7-month-old 3xTg-AD mice. Changes in binding parameters of [(3)H]-flunitrazepam to GABAA receptor and of [(3)H]-MK-801 to NMDA receptor in cerebral cortex of 3xTgAD mice were restored by voluntary exercise. In addition, reduced expression levels of NMDA receptor NR2B subunit were reestablished. The synaptic proteins synaptophysin and PSD-95 and the neuroprotective proteins GDNF and SIRT1 were downregulated in 3xTgAD mice and were recovered by exercise treatment. Overall, in this paper we highlight the fact that different interrelated mechanisms are involved in the beneficial effects of exercise on synaptic plasticity alterations in the 3xTg-AD mouse model.
Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS, Barcelona, Spain.
Susana
S
Revilla
Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS, Barcelona, Spain.
Cristina
C
Suñol
Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS, Barcelona, Spain.
Yoelvis
Y
García-Mesa
Institute of Neuroscience & Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona, Barcelona, Spain.
Lydia
L
Giménez-Llort
Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS, Barcelona, Spain.
Coral
C
Sanfeliu
Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC, IDIBAPS, Barcelona, Spain. Electronic address: rosa.cristofol@iibb.csic.es.
Rosa
R
Cristòfol
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000534:rehabilitation*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D005445:Flunitrazepam / Q000493:pharmacokinetics; D018757:GABA Modulators / Q000493:pharmacokinetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal / Q000379:methods*; D053764:Presenilin-1 / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D014316:Tritium / Q000493:pharmacokinetics
D016564:Amyloid beta-Protein Precursor; D051017:Apoptosis Regulatory Proteins; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; C121001:NR2B NMDA receptor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D005445:Flunitrazepam; D016291:Dizocilpine Maleate
3xTg-AD mouse; Alzheimer's disease; GABA and NMDA receptors; GDNF; SIRT1; Synaptic proteins; Voluntary exercise