000232662 001__ 232662
000232662 005__ 20190416055600.0
000232662 022__ $$a2045-2322
000232662 02470 $$2ISI$$a000417025400006
000232662 0247_ $$a10.1038/s41598-017-17201-8$$2doi
000232662 037__ $$aARTICLE
000232662 245__ $$aAerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse model of Down syndrome
000232662 269__ $$a2017
000232662 260__ $$c2017
000232662 300__ $$a22
000232662 336__ $$aJournal Articles
000232662 520__ $$aDown syndrome (DS) is caused by the triplication of human chromosome 21 and represents the most frequent genetic cause of intellectual disability. The trisomic Ts65Dn mouse model of DS shows synaptic deficits and reproduces the essential cognitive disabilities of the human syndrome. Aerobic exercise improved various neurophysiological dysfunctions in Ts65Dn mice, including hippocampal synaptic deficits, by promoting synaptogenesis and neurotransmission at glutamatergic terminals. Most importantly, the same intervention also prompted the recovery of hippocampal adult neurogenesis and synaptic plasticity and restored cognitive performance in trisomic mice. Additionally, the expression of brain-derived neurotrophic factor (BDNF) was markedly decreased in the hippocampus of patients with DS. Since the positive effect of exercise was paralleled by increased BDNF expression in trisomic mice, we investigated the effectiveness of a BDNF-mimetic treatment with 7,8-dihydroxyflavone at alleviating intellectual disabilities in the DS model. Pharmacological stimulation of BDNF signaling rescued synaptic plasticity and memory deficits in Ts65Dn mice. Based on our findings, Ts65Dn mice benefit from interventions aimed at promoting brain plasticity, and we provide evidence that BDNF signaling represents a potentially new pharmacological target for treatments aimed at rescuing cognitive disabilities in patients with DS.
000232662 700__ $$aParrini, Martina
000232662 700__ $$g254787$$aGhezzi, Diego$$0249241
000232662 700__ $$aDeidda, Gabriele
000232662 700__ $$aMedrihan, Lucian
000232662 700__ $$aCastroflorio, Enrico
000232662 700__ $$aAlberti, Micol
000232662 700__ $$aBaldelli, Pietro
000232662 700__ $$aCancedda, Laura
000232662 700__ $$aContestabile, Andrea
000232662 773__ $$k1$$j7$$tScientific Reports
000232662 8560_ $$fdiego.ghezzi@epfl.ch
000232662 8564_ $$uhttps://infoscience.epfl.ch/record/232662/files/Parrini%20et%20al.%2C%202017.pdf$$zFinal$$s9540895
000232662 8564_ $$uhttps://infoscience.epfl.ch/record/232662/files/Parrini%20et%20al.%2C%202017.pdf?subformat=pdfa$$zFinal$$s4812142$$xpdfa
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000232662 909CO $$ooai:infoscience.tind.io:232662$$qGLOBAL_SET$$pSTI$$particle
000232662 917Z8 $$x254787
000232662 917Z8 $$x254787
000232662 917Z8 $$x254787
000232662 937__ $$aEPFL-ARTICLE-232662
000232662 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000232662 980__ $$aARTICLE