scholarly journals Early-life environmental enrichment generates persistent individualized behavior in mice

2020 ◽  
Vol 6 (35) ◽  
pp. eabb1478 ◽  
Author(s):  
Sara Zocher ◽  
Susan Schilling ◽  
Anna N. Grzyb ◽  
Vijay S. Adusumilli ◽  
Jadna Bogado Lopes ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Environmental Enrichment ◽  
Brain Plasticity ◽  
Inbred Mice ◽  
Hippocampal Neurogenesis ◽  
Enriched Environment ◽  
Adult Hippocampal Neurogenesis ◽  
Shared Environment ◽  
The Stability

Individuals differ in their response to environmental stimuli, but the stability of individualized behaviors and their associated changes in brain plasticity are poorly understood. We developed a novel model of enriched environment to longitudinally monitor 40 inbred mice exploring 35 connected cages over periods of 3 to 6 months. We show that behavioral individuality that emerged during the first 3 months of environmental enrichment persisted when mice were withdrawn from the enriched environment for 3 additional months. Behavioral trajectories were associated with stable interindividual differences in adult hippocampal neurogenesis and persistent epigenetic effects on neuronal plasticity genes in the hippocampus. Using genome-wide DNA methylation sequencing, we show that one-third of the DNA methylation changes were maintained after withdrawal from the enriched environment. Our results suggest that, even under conditions that control genetic background and shared environment, early-life experiences result in lasting individualized changes in behavior, brain plasticity, and epigenetics.

scholarly journals Early-life environmental enrichment generates persistent individualized behavior in mice

2019 ◽  
Author(s):  
Sara Zocher ◽  
Susan Schilling ◽  
Anna N. Grzyb ◽  
Vijay S. Adusumilli ◽  
Jadna Bogado Lopes ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Environmental Enrichment ◽  
Brain Plasticity ◽  
Inbred Mice ◽  
Hippocampal Neurogenesis ◽  
Enriched Environment ◽  
Adult Hippocampal Neurogenesis ◽  
Genes And Environment ◽  
The Stability

AbstractIndividuals differ in their response to environmental stimuli, but the stability of individualized behaviors and their associated changes in brain plasticity are poorly understood. We developed a novel model of enriched environment to longitudinally monitor 40 inbred mice exploring 35 connected cages over periods of three to six months. We show that behavioral individuality that emerged during the first three months of environmental enrichment persisted when mice were withdrawn from the enriched environment for three additional months. Behavioral trajectories were associated with stable inter-individual differences in adult hippocampal neurogenesis and persistent epigenetic effects on neuronal plasticity genes in the hippocampus. Using genome-wide DNA methylation sequencing, we show that one third of the DNA methylation changes were maintained after withdrawal from the enriched environment. Our results suggest that, even under the most constraint conditions controlling genes and environment, early-life experiences result in lasting individualized changes in behavior and brain plasticity.

scholarly journals Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Zocher ◽  
Rupert W. Overall ◽  
Mathias Lesche ◽  
Andreas Dahl ◽  
Gerd Kempermann
Keyword(s):  
Dna Methylation ◽  
Brain Function ◽  
Environmental Enrichment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Aged Mouse ◽  
Lifestyle Interventions ◽  
Epigenetic Changes ◽  
Aging Effects ◽  
Age Related

AbstractThe decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.

scholarly journals Epigenetic rejuvenation of the hippocampus by environmental enrichment

2019 ◽  
Author(s):  
Sara Zocher ◽  
Rupert W. Overall ◽  
Mathias Lesche ◽  
Andreas Dahl ◽  
Gerd Kempermann
Keyword(s):  
Dna Methylation ◽  
Brain Function ◽  
Environmental Enrichment ◽  
Brain Aging ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Lifestyle Interventions ◽  
Epigenetic Changes ◽  
Aging Effects ◽  
Age Related

AbstractThe decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that environmental enrichment counteracted age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is known to control neuronal functions. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the rejuvenating effects of environmental enrichment at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.

Adult hippocampal neurogenesis: an important target associated with antidepressant effects of exercise

2017 ◽  
Vol 28 (7) ◽  
pp. 693-703 ◽  
Author(s):  
Lina Sun ◽  
Qingshan Sun ◽  
Jinshun Qi
Keyword(s):  
Adult Neurogenesis ◽  
Healthy Lifestyle ◽  
Brain Plasticity ◽  
Treatment Method ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Brain Functions ◽  
Antidepressant Effects ◽  
Exercise Activity ◽  
The Brain

AbstractDepression is a prevalent devastating mental disorder that affects the normal life of patients and brings a heavy burden to whole society. Although many efforts have been made to attenuate depressive/anxiety symptoms, the current clinic antidepressants have limited effects. Scientists have long been making attempts to find some new strategies that can be applied as the alternative antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been suggested as a therapy that can relieve psychiatric stress. However, how exercise improves the brain functions and reaches the antidepressant target needs systematic summarization due to the complexity and heterogeneous feature of depression. Brain plasticity, especially adult neurogenesis in the hippocampus, is an important neurophysiology to facilitate animals for neurogenesis can occur in not only humans. Many studies indicated that an appropriate level of exercise can promote neurogenesis in the adult brains. In this article, we provide information about the antidepressant effects of exercise and its implications in adult neurogenesis. From the neurogenesis perspective, we summarize evidence about the effects of exercise in enhancing neurogenesis in the hippocampus through regulating growth factors, neurotrophins, neurotransmitters and metabolism as well as inflammations. Taken together, a large number of published works indicate the multiple benefits of exercise in the brain functions of animals, particularly brain plasticity like neurogenesis and synaptogenesis. Therefore, a new treatment method for depression therapy can be developed by regulating the exercise activity.

scholarly journals Enriched Environment Ameliorates Adult Hippocampal Neurogenesis Deficits in Tcf4 Haploinsufficient Mice

2020 ◽  
Author(s):  
Katharina Braun ◽  
Benjamin M. Häberle ◽  
Marie-Theres Wittmann ◽  
Dieter Chichung Lie
Keyword(s):  
Transcription Factor ◽  
Intellectual Disability ◽  
Knockout Mice ◽  
Negative Impact ◽  
Brain Regions ◽  
Nervous System Development ◽  
Hippocampal Neurogenesis ◽  
Enriched Environment ◽  
Adult Hippocampal Neurogenesis ◽  
Wide Range

Abstract Background: Transcription factor 4 (TCF4) has been linked to human neurodevelopmental disorders such as intellectual disability, Pitt-Hopkins Syndrome (PTHS), autism, and schizophrenia. Recent work demonstrated that TCF4 participates in the control of a wide range of neurodevelopmental processes in mammalian nervous system development including neural precursor proliferation, timing of differentiation, migration, dendritogenesis and synapse formation. TCF4 is highly expressed in the adult hippocampal dentate gyrus – one of the few brain regions where neural stem / progenitor cells generate new functional neurons throughout life.Results: We here investigated whether TCF4 haploinsufficiency, which in humans causes non-syndromic forms of intellectual disability and PTHS, affects adult hippocampal neurogenesis, a process that is essential for hippocampal plasticity in rodents and potentially in humans. Young adult Tcf4 heterozygote knockout mice showed a major reduction in the level of adult hippocampal neurogenesis, which was at least in part caused by lower stem/progenitor cell numbers and impaired maturation and survival of adult-generated neurons. Interestingly, housing in an enriched environment was sufficient to enhance maturation and survival of new neurons and to substantially augment neurogenesis levels in Tcf4 heterozygote knockout mice.Conclusion: Haploinsufficiency for the transcription factor TCF4 has been linked to non-syndromic intellectual disability and PTHS. The present findings raise the possibility that TCF4 haploinsufficiency may have a continuous negative impact on hippocampal function by impeding hippocampal neurogenesis and suggest that behavioural stimulation may be harnessed to ameliorate a subset of TCF4 haploinsufficiency associated neural deficits during adulthood.

scholarly journals Circulating unacylated-ghrelin impairs hippocampal neurogenesis and memory in mice and is altered in human Parkinson's disease dementia

2018 ◽  
Author(s):  
Amanda K E Hornsby ◽  
Vanessa V Santos ◽  
Fionnuala Johnston ◽  
Luke D Roberts ◽  
Romana Stark ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Plasticity ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Unexpected Finding ◽  
Unacylated Ghrelin ◽  
Memory Impairments ◽  
Acyl Ghrelin

Blood-borne factors regulate adult hippocampal neurogenesis (AHN) and cognition in mammals, albeit via mechanisms that are poorly understood. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in GOAT-/- mice that lack acyl-ghrelin (AG) but have high levels of UAG, were rescued by treatment with AG. This unexpected finding suggests that the post-translational acylation of ghrelin is an important modulator of neurogenesis and memory in adult mammals. To determine whether this paradigm is relevant to humans we analysed circulating AG:UAG levels in Parkinson's disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients and healthy controls. Uniquely, the ratio of plasma AG:UAG was reduced in the PDD cohort and correlated with cognitive performance. Our results identify UAG as a novel regulator of neurogenesis and cognition, and AG:UAG as a circulating diagnostic biomarker of dementia. The findings extend our understanding of adult brain plasticity regulation by circulating factors and suggest that manipulating the post-translational acylation of plasma ghrelin may offer therapeutic opportunities to ameliorate cognitive decline.

scholarly journals The Effects of Early Life Stress on the Brain and Behaviour: Insights From Zebrafish Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Helen Eachus ◽  
Min-Kyeung Choi ◽  
Soojin Ryu
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Brain Regions ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Current Status ◽  
Comprehensive Overview ◽  
Behavioural Changes ◽  
The Brain

The early life period represents a window of increased vulnerability to stress, during which exposure can lead to long-lasting effects on brain structure and function. This stress-induced developmental programming may contribute to the behavioural changes observed in mental illness. In recent decades, rodent studies have significantly advanced our understanding of how early life stress (ELS) affects brain development and behaviour. These studies reveal that ELS has long-term consequences on the brain such as impairment of adult hippocampal neurogenesis, altering learning and memory. Despite such advances, several key questions remain inadequately answered, including a comprehensive overview of brain regions and molecular pathways that are altered by ELS and how ELS-induced molecular changes ultimately lead to behavioural changes in adulthood. The zebrafish represents a novel ELS model, with the potential to contribute to answering some of these questions. The zebrafish offers some important advantages such as the ability to non-invasively modulate stress hormone levels in a whole animal and to visualise whole brain activity in freely behaving animals. This review discusses the current status of the zebrafish ELS field and its potential as a new ELS model.

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