Dissociating the therapeutic effects of environmental enrichment and exercise in a mouse model of anxiety with cognitive impairment

Abstract

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.

Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes

“…However, it would also be important to contrast our environmental enrichment protocol with that of Gapp et al (2016), which provided running wheels. Our laboratory, and others, have demonstrated dissociable effects of environmental enrichment and running on behavior and hippocampal gene expression (Grégoire et al, 2014;Mustroph et al, 2016;Rogers et al, 2016;Zajac et al, 2010); thus, it would be reasonable to speculate that offspring hippocampal GR expression is not influenced under our experimental conditions.…”

“…Environmental enrichment (EE) is an experimental paradigm that has been shown to limit behavioral, cellular and molecular pathologies in various disease models, including models of stress (Chekmareva et al, 2014;Renoir et al, 2013;Rogers et al, 2016). EE rescues the depression-like phenotype and corrects HPA-axis dysregulation in a mouse model of alcohol withdrawal .…”

Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD

“…Additionally, the use of different developmental deficits is greatly encouraged, as this will assist in developing effective therapeutic interventions for individuals afflicted by such disorders. Previous literature has demonstrated independent effects of WR or EC on adult neurogenesis, learning and memory, or anxiety-like behaviors in a genetic mouse model of anxiety 53 . The robustness of these two interventions and the synergistic effect of EC to sustain the short-term effects of increased WR-induced benefits ( i.e.…”

Environmental Enrichment Improves Spatial Learning and Memory in Vascular Dementia Rats with Activation of Wnt/β-Catenin Signal Pathway

“…Recently, Choi et al found that exercise could delay cognitive decline by enhancing neurogenesis and increasing BDNF expression in the context of VaD [37]. Rogers et al found exercise (Ex) and EE (without exercise) had different effects in a mouse model of anxiety with cognitive impairment, and corrected long-term spatial memory deficits are related to Ex, but not the 2 other parts of EE [38]. Sozda et al demonstrated that exposing TBI rats to any of the 3 components individually may be more advantageous than no enrichment, but only exposure to typical EE yields optimal benefits.…”