Dissociating the therapeutic effects of environmental enrichment and exercise in a mouse model of anxiety with cognitive impairment.
Clinical evidence indicates that serotonin-1A receptor (5-HT1AR) gene polymorphisms are associated with anxiety disorders and deficits in cognition. In animal models, exercise (Ex) and environmental enrichment (EE) can change emotionality-related behaviours, as well as enhance some aspects of cognition and hippocampal neurogenesis. We investigated the effects of Ex and EE (which does not include running wheels) on cognition and anxiety-like behaviours in wild-type (WT) and 5-HT1AR knock-out (KO) mice. Using an algorithm-based classification of search strategies in the Morris water maze, we report for we believe the first time that Ex increased the odds for mice to select more hippocampal-dependent strategies. In the retention probe test, Ex (but not EE) corrected long-term spatial memory deficits displayed by KO mice. In agreement with these findings, only Ex increased hippocampal cell survival and BDNF protein levels. However, only EE (but not Ex) modified anxiety-like behaviours, demonstrating dissociation between improvements in cognition and innate anxiety. EE enhanced hippocampal cell proliferation in WT mice only, suggesting a crucial role for intact serotonergic signalling in mediating this effect. Together, these results demonstrate differential effects of Ex vs EE in a mouse model of anxiety with cognitive impairment. Overall, the 5-HT1AR does not seem to be critical for those behavioural effects to occur. These findings will have implications for our understanding of how Ex and EE enhance experience-dependent plasticity, as well as their differential impacts on anxiety and cognition.
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.
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J
Rogers
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.
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Vo
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.|School of Psychology and Public Health, La Trobe University, Bundoora, VIC, Australia.
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Buret
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.
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Pang
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.
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Meiklejohn
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.
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Zeleznikow-Johnston
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.|School of Mathematical and Geospatial Sciences, RMIT University, Melbourne, VIC, Australia.
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Churilov
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.|School of Psychology and Public Health, La Trobe University, Bundoora, VIC, Australia.
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van den Buuse
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.|Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia.
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AJ
Hannan
Gene Environment & Behaviour Laboratory, Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, Australia.
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Renoir
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D004195:Disease Models, Animal; D004777:Environment; D006624:Hippocampus / Q000503:physiopathology; D018782:Maze Learning / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal; D016133:Polymerase Chain Reaction