Effects of voluntary physical exercise on adult hippocampal neurogenesis and behavior of Ts65Dn mice, a model of Down syndrome

Abstract The Ts65Dn (TS) mouse is the most widely used model of Down syndrome (DS). This mouse shares many phenotypic characteristics with the human condition including cognitive and neuromorphological alterations. In this study the effects of physical exercise on hippocampal neurogenesis and behavi...

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Published in:	Neuroscience Vol. 171; no. 4; pp. 1228 - 1240
Main Authors:	Llorens-Martín, M.V, Rueda, N, Tejeda, G.S, Flórez, J, Trejo, J.L, Martínez-Cué, C
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 29-12-2010 Elsevier
Subjects:	Analysis of Variance Animals Apoptosis Biological and medical sciences Bromodeoxyuridine - metabolism Cell Count - methods Cell Proliferation Chromosome aberrations cognition Down syndrome Down Syndrome - genetics Down Syndrome - pathology Down Syndrome - physiopathology Down Syndrome - rehabilitation exercise Fundamental and applied biological sciences. Psychology Hippocampus - pathology Hippocampus - physiopathology Maze Learning - physiology Medical genetics Medical sciences Mice Mice, Inbred C57BL Mice, Transgenic Microtubule-Associated Proteins - metabolism Neurogenesis - physiology Neurology Neurons - metabolism Neuropeptides - metabolism Physical Conditioning, Animal - physiology postnatal neurogenesis Swimming - psychology Vertebrates: nervous system and sense organs long term potentiation doublecortin DG cognition apoptosis exercise control mice LTP Down syndrome postnatal neurogenesis CO 5-bromo-2-deoxyuridine DS Ts65Dn mouse dentate gyrus phospho histone 3 DCX PH3 BrdU TS Chromosomal aberration Physical exercise Animal model Trisomy Rodentia Central nervous system Aneuploidy Cognition Neurogenesis Encephalon Vertebrata Mammalia Mouse Cell death Animal Behavior Hippocampus Apoptosis
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Summary:	Abstract The Ts65Dn (TS) mouse is the most widely used model of Down syndrome (DS). This mouse shares many phenotypic characteristics with the human condition including cognitive and neuromorphological alterations. In this study the effects of physical exercise on hippocampal neurogenesis and behavior in TS mice were assessed. 10–12 month-old male TS and control (CO) mice were submitted to voluntary physical exercise for 7 weeks and the effects of this protocol on hippocampal morphology, neurogenesis and apoptosis were evaluated. Physical exercise improved performance in the acquisition sessions of the Morris water maze in TS but not in CO mice. Conversely, it did not have any effect on anxiety or depressive behavior in TS mice but it did reduce the cognitive components of anxiety in CO mice. TS mice presented a reduced dentate gyrus (DG) volume, subgranular zone area and number of granule neurons. Hippocampal neurogenesis was reduced in TS mice as shown by the reduced number of 5-bromo-2-deoxyuridine (BrdU) positive cells. Voluntary physical exercise did not rescue these alterations in TS mice but it did increase the number of doublecortin (DCX)-and phospho histone 3 (PH3)-positive neurons in CO mice. It is concluded that physical exercise produced a modest anxiolytic effect in CO mice and that this was accompanied by an increased number of immature cells in the hippocampal DG. On the other hand, voluntary physical exercise exerted a positive effect on TS mice learning of the platform position in the Morris water maze that seems to be mediated by a neurogenesis-independent mechanism.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2010.09.043