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individuality that emerged during the first three months of environmental enrichment persisted when mice were withdrawn from the enriched environment for three additional months.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 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 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 Awareness of maternal stress, consequences for the offspring and the need for early interventions to increase stress resilience

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Birgit Arabin ◽  
Lars Hellmeyer ◽  
Johanna Maul ◽  
Gerlinde A.S. Metz
Keyword(s):  
Life Stress ◽  
Maternal Stress ◽  
Brain Plasticity ◽  
Hippocampal Neurogenesis ◽  
Enriched Environment ◽  
Fertility Treatment ◽  
Vulnerable Groups ◽  
Environment Change ◽  
Stress Resilience ◽  
Genes And Environment

Abstract Experimental and clinical studies suggest that prenatal experiences may influence health trajectories up to adulthood and high age. According to the hypothesis of developmental origins of health and disease exposure of pregnant women to stress, nutritional challenges, infection, violence, or war may “program” risks for diseases in later life. Stress and anxieties can exist or be provoked in parents after fertility treatment, after information or diagnosis of fetal abnormalities and demand simultaneous caring concepts to support the parents. In vulnerable groups, it is therefore important to increase the stress resilience to avoid harmful consequences for the growing child. “Enriched environment” defines a key paradigm to decipher how interactions between genes and environment change the structure and function of the brain. The regulation of the fetal hippocampal neurogenesis and morphology during pregnancy is one example of this complex interaction. Animal experiments have demonstrated that an enriched environment can revert consequences of stress in the offspring during critical periods of brain plasticity. Epigenetic markers of stress or wellbeing during pregnancy might even be diagnosed by fragments of placental DNA in the maternal circulation that show characteristic methylation patterns. The development of fetal senses further illustrates how external stimulation may impact individual preferences. Here, we therefore not only discuss how maternal stress influences cognitive development and resilience, but also design possibilities of non-invasive interventions for both mothers and children summarized and evaluated in the light of their potential to improve the health of future generations.

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.

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