PMID- 29203796
OWN - NLM
STAT- MEDLINE
DCOM- 20190705
LR  - 20190705
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Dec 4
TI  - Aerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse 
      model of Down syndrome.
PG  - 16825
LID - 10.1038/s41598-017-17201-8 [doi]
LID - 16825
AB  - Down 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.
FAU - Parrini, Martina
AU  - Parrini M
AD  - Department of Neuroscience and Brain Technologies, Istituto Italiano di 
      Tecnologia, Genova, Italy.
FAU - Ghezzi, Diego
AU  - Ghezzi D
AUID- ORCID: 0000-0002-0554-7510
AD  - Department of Neuroscience and Brain Technologies, Istituto Italiano di 
      Tecnologia, Genova, Italy.
AD  - Medtronic Chair in Neuroengineering, Center for Neuroprosthetics, Institute of 
      Bioengineering, School of Engineering, Ecole Polytechnique Federale de Lausanne, 
      Lausanne, Switzerland.
FAU - Deidda, Gabriele
AU  - Deidda G
AD  - Department of Neuroscience and Brain Technologies, Istituto Italiano di 
      Tecnologia, Genova, Italy.
AD  - Laboratory of Neurophysiology, Department of Physiology and Biochemistry, 
      University of Malta, Msida, Malta.
FAU - Medrihan, Lucian
AU  - Medrihan L
AD  - Department of Neuroscience and Brain Technologies, Istituto Italiano di 
      Tecnologia, Genova, Italy.
AD  - Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New 
      York, NY, USA.
FAU - Castroflorio, Enrico
AU  - Castroflorio E
AD  - Center for Synaptic Neuroscience, Istituto Italiano di Tecnologia, Genova, Italy.
FAU - Alberti, Micol
AU  - Alberti M
AD  - Department of Neuroscience and Brain Technologies, Istituto Italiano di 
      Tecnologia, Genova, Italy.
FAU - Baldelli, Pietro
AU  - Baldelli P
AUID- ORCID: 0000-0001-9599-3436
AD  - Center for Synaptic Neuroscience, Istituto Italiano di Tecnologia, Genova, Italy.
AD  - Department of Experimental Medicine, University of Genova, Genova, Italy.
FAU - Cancedda, Laura
AU  - Cancedda L
AUID- ORCID: 0000-0003-0566-057X
AD  - Department of Neuroscience and Brain Technologies, Istituto Italiano di 
      Tecnologia, Genova, Italy.
FAU - Contestabile, Andrea
AU  - Contestabile A
AUID- ORCID: 0000-0002-5417-4722
AD  - Department of Neuroscience and Brain Technologies, Istituto Italiano di 
      Tecnologia, Genova, Italy. andrea.contestabile@iit.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171204
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Flavones)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Down Syndrome/drug therapy/*pathology
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Female
MH  - Flavones/*pharmacology/therapeutic use
MH  - Hippocampus/metabolism/pathology
MH  - Humans
MH  - Learning/*drug effects
MH  - Male
MH  - Memory/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neurogenesis
MH  - Neuronal Plasticity/drug effects
MH  - Physical Conditioning, Animal
MH  - Signal Transduction/drug effects
PMC - PMC5715062
COIS- The authors declare that they have no competing interests.
EDAT- 2017/12/06 06:00
MHDA- 2019/07/06 06:00
PMCR- 2017/12/04
CRDT- 2017/12/06 06:00
PHST- 2017/06/14 00:00 [received]
PHST- 2017/11/23 00:00 [accepted]
PHST- 2017/12/06 06:00 [entrez]
PHST- 2017/12/06 06:00 [pubmed]
PHST- 2019/07/06 06:00 [medline]
PHST- 2017/12/04 00:00 [pmc-release]
AID - 10.1038/s41598-017-17201-8 [pii]
AID - 17201 [pii]
AID - 10.1038/s41598-017-17201-8 [doi]
PST - epublish
SO  - Sci Rep. 2017 Dec 4;7(1):16825. doi: 10.1038/s41598-017-17201-8.