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Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress.

Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M - Mol. Psychiatry (2010)

Bottom Line: It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression.Our data show two main findings.First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Pathophysiology, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

ABSTRACT
The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

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Related in: MedlinePlus

Control and NG- mice show no differences in baseline physiology, no changes in baseline behavioral tests for locomotion, anxiety and depressive-like behavior, and no difference in olfactory habituation/dishabituation. hGFAPtk mice treated for 8 weeks with VGCV (NG-) do not show any differences in body weights (a), motor strength in the wire hang test (b) or novel cage stress-induced hyperthermia (c). NG- mice do not differ from controls in activity in or habituation to an open field (d), show no differences in anxiety or exploration in the open field or light–dark box test (d and e) and have normal saccharine preference (f). NG- mice do not differ from controls in an olfactory habituation dishabituation test for standard odors (g) nor for odors carrying a social connotation (h). Cotton tips dipped in different odors; water (w1-3), banana (b1-3), almond (a1-3) and imitation almond (ia1-3) were introduced to the animals homecage three consecutive times for 3 min. Both NG- and control mice spend the same amount of time sniffing and habituating to the different odors (g). Similarly, no difference was found between control and NG- mice sniffing and habituating to cotton tips dipped in urine from female animals in non-estrous (NE) or estrous (E) phase of their estrous cycle as well as urine from dominant (Dom) CD-1 animals and subordinate (Sub) C57Bl/6J animals (h).
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fig2: Control and NG- mice show no differences in baseline physiology, no changes in baseline behavioral tests for locomotion, anxiety and depressive-like behavior, and no difference in olfactory habituation/dishabituation. hGFAPtk mice treated for 8 weeks with VGCV (NG-) do not show any differences in body weights (a), motor strength in the wire hang test (b) or novel cage stress-induced hyperthermia (c). NG- mice do not differ from controls in activity in or habituation to an open field (d), show no differences in anxiety or exploration in the open field or light–dark box test (d and e) and have normal saccharine preference (f). NG- mice do not differ from controls in an olfactory habituation dishabituation test for standard odors (g) nor for odors carrying a social connotation (h). Cotton tips dipped in different odors; water (w1-3), banana (b1-3), almond (a1-3) and imitation almond (ia1-3) were introduced to the animals homecage three consecutive times for 3 min. Both NG- and control mice spend the same amount of time sniffing and habituating to the different odors (g). Similarly, no difference was found between control and NG- mice sniffing and habituating to cotton tips dipped in urine from female animals in non-estrous (NE) or estrous (E) phase of their estrous cycle as well as urine from dominant (Dom) CD-1 animals and subordinate (Sub) C57Bl/6J animals (h).

Mentions: No unwanted side effects that could compromise the general health of the animal were apparent in VGCV-treated hGFAPtk mice. No changes were detected in NG- mice in any parameters of a comprehensive physical examination that included physical characteristics, general behavioral observations, sensorimotor reflexes and motor responses (Supplementary Table 1). An extensive pathological examination of hGFAPtk mice after prolonged (>8 weeks) VGCV treatment did not reveal any functionally significant effects of the antiviral drug treatment (pathology reports are provided as Supplementary Material). No differences in body weight, motor strength or stress-induced hyperthermia were detected in VGCV-treated hGFAPtk mice lacking neurogenesis even after prolonged VGCV treatment (>8 weeks) (Figure 2a, b and c). Baseline behavior of NG- mice compared with controls differed neither in measurements of locomotion and exploration, nor in anxiety and hedonic drive (Figure 2d, e and f).


Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress.

Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M - Mol. Psychiatry (2010)

Control and NG- mice show no differences in baseline physiology, no changes in baseline behavioral tests for locomotion, anxiety and depressive-like behavior, and no difference in olfactory habituation/dishabituation. hGFAPtk mice treated for 8 weeks with VGCV (NG-) do not show any differences in body weights (a), motor strength in the wire hang test (b) or novel cage stress-induced hyperthermia (c). NG- mice do not differ from controls in activity in or habituation to an open field (d), show no differences in anxiety or exploration in the open field or light–dark box test (d and e) and have normal saccharine preference (f). NG- mice do not differ from controls in an olfactory habituation dishabituation test for standard odors (g) nor for odors carrying a social connotation (h). Cotton tips dipped in different odors; water (w1-3), banana (b1-3), almond (a1-3) and imitation almond (ia1-3) were introduced to the animals homecage three consecutive times for 3 min. Both NG- and control mice spend the same amount of time sniffing and habituating to the different odors (g). Similarly, no difference was found between control and NG- mice sniffing and habituating to cotton tips dipped in urine from female animals in non-estrous (NE) or estrous (E) phase of their estrous cycle as well as urine from dominant (Dom) CD-1 animals and subordinate (Sub) C57Bl/6J animals (h).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2990187&req=5

fig2: Control and NG- mice show no differences in baseline physiology, no changes in baseline behavioral tests for locomotion, anxiety and depressive-like behavior, and no difference in olfactory habituation/dishabituation. hGFAPtk mice treated for 8 weeks with VGCV (NG-) do not show any differences in body weights (a), motor strength in the wire hang test (b) or novel cage stress-induced hyperthermia (c). NG- mice do not differ from controls in activity in or habituation to an open field (d), show no differences in anxiety or exploration in the open field or light–dark box test (d and e) and have normal saccharine preference (f). NG- mice do not differ from controls in an olfactory habituation dishabituation test for standard odors (g) nor for odors carrying a social connotation (h). Cotton tips dipped in different odors; water (w1-3), banana (b1-3), almond (a1-3) and imitation almond (ia1-3) were introduced to the animals homecage three consecutive times for 3 min. Both NG- and control mice spend the same amount of time sniffing and habituating to the different odors (g). Similarly, no difference was found between control and NG- mice sniffing and habituating to cotton tips dipped in urine from female animals in non-estrous (NE) or estrous (E) phase of their estrous cycle as well as urine from dominant (Dom) CD-1 animals and subordinate (Sub) C57Bl/6J animals (h).
Mentions: No unwanted side effects that could compromise the general health of the animal were apparent in VGCV-treated hGFAPtk mice. No changes were detected in NG- mice in any parameters of a comprehensive physical examination that included physical characteristics, general behavioral observations, sensorimotor reflexes and motor responses (Supplementary Table 1). An extensive pathological examination of hGFAPtk mice after prolonged (>8 weeks) VGCV treatment did not reveal any functionally significant effects of the antiviral drug treatment (pathology reports are provided as Supplementary Material). No differences in body weight, motor strength or stress-induced hyperthermia were detected in VGCV-treated hGFAPtk mice lacking neurogenesis even after prolonged VGCV treatment (>8 weeks) (Figure 2a, b and c). Baseline behavior of NG- mice compared with controls differed neither in measurements of locomotion and exploration, nor in anxiety and hedonic drive (Figure 2d, e and f).

Bottom Line: It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression.Our data show two main findings.First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Pathophysiology, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

ABSTRACT
The subgranular zone of the adult hippocampal dentate gyrus contains a pool of neural stem cells that continuously divide and differentiate into functional granule cells. It has been shown that production of new hippocampal neurons is necessary for amelioration of stress-induced behavioral changes by antidepressants in animal models of depression. The survival of newly born hippocampal neurons is decreased by chronic psychosocial stress and increased by exposure to enriched environments. These observations suggest the existence of a link between hippocampal neurogenesis, stress-induced behavioral changes, and the beneficial effects of enriched environment. To show causality, we subjected transgenic mice with conditionally suppressed neurogenesis to psychosocial stress followed by environmental enrichment. First, we showed that repeated social defeat coupled with chronic exposure to an aggressor produces robust and quantifiable indices of submissive and depressive-like behaviors; second, subsequent exposure to an enriched environment led to extinction of the submissive phenotype, while animals exposed to an impoverished environment retained the submissive phenotype; and third, enrichment was not effective in reversing the submissive and depressive-like behaviors in transgenic mice lacking neurogenesis. Our data show two main findings. First, living in an enriched environment is highly effective in extinguishing submissive behavioral traits developed during chronic social stress, and second, these effects are critically dependent on adult neurogenesis, indicating that beneficial behavioral adaptations are dependent on intact adult neurogenesis.

Show MeSH
Related in: MedlinePlus