Calmodulin activation is required for the enhancement of hippocampal neurogenesis following environmental enrichment

Depression is a neuropsychiatric disorder with a high impact on the worldwide population. To overcome depression, antidepressant drugs are the first line of treatment. However, pre-clinical studies have pointed out that antidepressants are not entirely efficacious and that the quality of the living environment after stress cessation may play a relevant role in increasing their efficacy. As it is unknown whether a short daily exposure to environmental enrichment during chronic stress and antidepressant treatment will be more effective than just the pharmacological treatment, this study analyzed the effects of fluoxetine, environmental enrichment, and their combination on depressive-associated behavior. Additionally, we investigated hippocampal neurogenesis in mice exposed to chronic mild stress. Our results indicate that fluoxetine reversed anhedonia. Besides, fluoxetine reversed the decrement of some events of the hippocampal neurogenic process caused by chronic mild stress. Conversely, short daily exposure to environmental enrichment changed the deterioration of the coat and anhedonia. Although, this environmental intervention did not produce significant changes in the neurogenic process affected by chronic mild stress, fluoxetine plus environmental enrichment showed similar effects to those caused by environmental enrichment to reverse depressive-like behaviors. Like fluoxetine, the combination reversed the declining number of Ki67, doublecortin, calretinin cells and mature newborn neurons. Finally, this study suggests that short daily exposure to environmental enrichment improves the effects of fluoxetine to reverse the deterioration of the coat and anhedonia in chronically stressed mice. In addition, the combination of fluoxetine with environmental enrichment produces more significant effects than those caused by fluoxetine alone on some events of the neurogenic process. Thus, environmental enrichment improves the benefits of pharmacological treatment by mechanisms that need to be clarified.

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Environmental Enrichment Protects Offspring of a Rat Model of Preeclampsia from Cognitive Decline

10.21203/rs.3.rs-736215/v1 ◽

2021 ◽

Author(s):

Huiqing Lu ◽

Lili Gong ◽

Huangfang Xu ◽

Qiongjie Zhou ◽

Huanqiang Zhao ◽

...

Keyword(s):

Synaptic Plasticity ◽

Cognitive Ability ◽

Inflammatory Cytokines ◽

Spatial Learning ◽

Rat Model ◽

Environmental Enrichment ◽

Inflammatory Cytokine ◽

Hippocampal Neurogenesis ◽

Expression Levels ◽

Cytokine Levels

Abstract Background Preeclampsia affects 5–8% of all pregnancies and contributes to adverse pregnancy and birth outcomes. In addition to the short-term effects of preeclampsia, preeclampsia can exert long-term adverse effects on offspring. Numerous studies have demonstrated that offspring of preeclamptic women exhibit cognitive deficits from childhood to old age. However, effective ways to improve the cognitive abilities of these offspring remain to be investigated. The aim of this study was to explore whether environmental enrichment in early life could restore the cognitive ability of the offspring of a rat model of preeclampsia and to investigate the cellular and molecular mechanisms by which EE improves cognitive ability. Methods L-NAME was used to establish a rat model of preeclampsia. The spatial learning and memory abilities and recognition memory of 56-day-old offspring were evaluated by the Morris water maze and Novel object recognition (NOR) task. Immunofluorescence was performed to evaluate cell proliferation and apoptosis in the DG region of the hippocampus. qRT-PCR was performed to examine the expression levels of neurogenesis-associated genes, pre- and postsynaptic proteins and inflammatory cytokines. An enzyme-linked immune absorbent assay was performed to evaluate the concentration of vascular endothelial growth factor (VEGF) and inflammatory cytokines in the hippocampus. Results The administration of L-NAME led to increased systolic blood pressure and urine protein levels in pregnant rats. Offspring in the L-NAME group exhibited impaired spatial learning ability and memory as well as NOR memory. Hippocampal neurogenesis and synaptic plasticity were impaired in offspring from the L-NAME group. Furthermore, cell apoptosis in the hippocampus was increased in the L-NAME group. The hippocampus was skewed to a proinflammatory profile, as shown by increased inflammatory cytokine levels. EE improved the cognitive ability of offspring in the L-NAME group and resulted in increased hippocampal neurogenesis and synaptic protein expression levels and decreased apoptosis and inflammatory cytokine levels. Conclusions Environmental enrichment resolves cognitive impairment in the offspring of a rat model of preeclampsia by improving hippocampal neurogenesis and synaptic plasticity and normalizing the apoptosis level and the inflammatory balance.

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Selective increases in inter-individual variability in response to environmental enrichment in female mice

eLife ◽

10.7554/elife.35690 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 12

Author(s):

Julia C Körholz ◽

Sara Zocher ◽

Anna N Grzyb ◽

Benjamin Morisse ◽

Alexandra Poetzsch ◽

...

Keyword(s):

Environmental Enrichment ◽

Specific Activity ◽

Individual Variability ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Multiple Parameters ◽

Wide Range ◽

Suitable Animal Model ◽

Brain And Behavior ◽

And Behavior

One manifestation of individualization is a progressively differential response of individuals to the non-shared components of the same environment. Individualization has practical implications in the clinical setting, where subtle differences between patients are often decisive for the success of an intervention, yet there has been no suitable animal model to study its underlying biological mechanisms. Here we show that enriched environment (ENR) can serve as a model of brain individualization. We kept 40 isogenic female C57BL/6JRj mice for 3 months in ENR and compared these mice to an equally sized group of standard-housed control animals, looking at the effects on a wide range of phenotypes in terms of both means and variances. Although ENR influenced multiple parameters and restructured correlation patterns between them, it only increased differences among individuals in traits related to brain and behavior (adult hippocampal neurogenesis, motor cortex thickness, open field and object exploration), in agreement with the hypothesis of a specific activity-dependent development of brain individuality.

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