Neurological conditions,including cognitive impairment and Alzheimer’s disease(AD),impose a huge burden on society,affecting millions of people globally.In addition to genetic factors,recent studies indicate that env...Neurological conditions,including cognitive impairment and Alzheimer’s disease(AD),impose a huge burden on society,affecting millions of people globally.In addition to genetic factors,recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases.Early life adversity(ELA)has a profound impact on brain function and health later in life.In rodent models,exposure to ELA results in specific cognitive deficits and aggravated AD pathology.Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people with a history of ELA.In this review,we scrutinize findings from human and animal studies focusing on the connection of ELA with cognitive impairment and AD.These discoveries suggest that ELA,especially at early postnatal stages,increases susceptibility to cognitive impairment and AD later in life.In terms of mechanisms,ELA could lead to dysregulation of the hypothalamus-pituitary-adrenal axis,altered gut microbiome,persistent inflammation,oligodendrocyte dysfunction,hypomyelination,and aberrant adult hippocampal neurogenesis.Crosstalks among these events may synergistically contribute to cognitive impairment later in life.Additionally,we discuss several interventions that may alleviate adverse consequences of ELA.Further investigation into this crucial area will help improve ELA management and reduce the burden of related neurological conditions.展开更多
The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with dif...The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome？ DNA methylation is an enzymatically- catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.展开更多
基金supported by the National Institute on Aging of the National Institutes of Health under Award Number RF1AG058603.
文摘Neurological conditions,including cognitive impairment and Alzheimer’s disease(AD),impose a huge burden on society,affecting millions of people globally.In addition to genetic factors,recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases.Early life adversity(ELA)has a profound impact on brain function and health later in life.In rodent models,exposure to ELA results in specific cognitive deficits and aggravated AD pathology.Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people with a history of ELA.In this review,we scrutinize findings from human and animal studies focusing on the connection of ELA with cognitive impairment and AD.These discoveries suggest that ELA,especially at early postnatal stages,increases susceptibility to cognitive impairment and AD later in life.In terms of mechanisms,ELA could lead to dysregulation of the hypothalamus-pituitary-adrenal axis,altered gut microbiome,persistent inflammation,oligodendrocyte dysfunction,hypomyelination,and aberrant adult hippocampal neurogenesis.Crosstalks among these events may synergistically contribute to cognitive impairment later in life.Additionally,we discuss several interventions that may alleviate adverse consequences of ELA.Further investigation into this crucial area will help improve ELA management and reduce the burden of related neurological conditions.
基金supported by a grant from the Canadian Institute of Health Research to M.S. M.Ssupported by the Sackler program in epigenetics and psychobiology at McGill University,Canada
文摘The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome？ DNA methylation is an enzymatically- catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.
