Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons

Kronman, Hope; Torres‐Berrío, Angélica; Sidoli, Simone; Issler, Orna; Godino, Arthur; Ramakrishnan, Aarthi; Mews, Philipp; Lardner, Casey K.; Parise, Eric M.; Walker, Deena M.; Zee, Yentl Y. van der; Browne, Caleb J.; Boyce, Brittany F.; Neve, Rachael L.; García, Benjamin A.; Shen, Li; Peña, Catherine J.; Nestler, Eric J.

doi:10.1038/s41593-021-00814-8

Cited by 69 publications

(72 citation statements)

References 56 publications

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“…However, most studies explore general epigenetic abnormalities in MDD, lacking the sexual and behavioral specificity. Various rodent models provide powerful tools to ameliorate specific aspects of different depression-like phenotypes ( Catale et al, 2020 ; Chang et al, 2020 ; Lei et al, 2020 ; Kronman et al, 2021 ). For example, social deficits in MDD are easily and superiorly recapitulated in the ELS models with maternal separation and social isolation paradigms.…”

Section: Discussionmentioning

confidence: 99%

“…Rodents subjected to more intense maternal separation exhibited more significant behavior changes in anxiety, depression and contextual fear memory, correlated with more diminished BDNF mRNA and protein levels, decreased H3K9 acetylation and increased HDAC2 levels in the hippocampus ( Sun et al, 2021 ). Mice subjected to postnatal maternal separation and then CSDS in adulthood displayed increased susceptibility to CSDS, along with trimethylation of the 4th lysine residue of histone H3 (H3K4me3) in the PFC ( Reshetnikov et al, 2021 ), and dimethylation of lysine 79 of histone H3 (H3K79me2) in the NAc ( Kronman et al, 2021 ).…”

Section: Epigenetic Regulation and Sex Differences In Animal Models Of Major Depressive Disorder Relevant To Social Behaviormentioning

confidence: 99%

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A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies

Cahill

Poelker-Wells

Prather

et al. 2021

Front. Neural Circuits

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Depression is an umbrella term used to describe a mood disorder with a broad spectrum of symptoms including a persistent feeling of sadness, loss of interest, and deficits in social behavior. Epigenetic research bridges the environmental and genetic landscape and has the potential to exponentially improve our understanding of such a complex disorder. Depression is also a sexually dimorphic disorder and variations exist within epigenetic modification sites between sexes. These sex-specific mediators may impact behavioral symptomology and could serve as therapeutic targets for treatments to improve behavioral deficits. This mini review will focus on the social behavior perspective of depression and specifically explore the sexually different epigenetic modifications on depression.

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Section: Discussionmentioning

confidence: 99%

Section: Epigenetic Regulation and Sex Differences In Animal Models Of Major Depressive Disorder Relevant To Social Behaviormentioning

confidence: 99%

A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies

Cahill

Poelker-Wells

Prather

et al. 2021

Front. Neural Circuits

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“…Several studies point to the effects of fetal programming and maternal and environmental factors during early life on the development of diseases in adulthood (11)(12)(13)(14)(15)(16). Maternal nutrition even before pregnancy can affect the development of the fetus with later risk for cardiovascular/metabolic diseases (12).…”

Section: Impact Of Nutritional Transition In Developing Countriesmentioning

confidence: 99%

The Transition From Undernutrition to Overnutrition Under Adverse Environments and Poverty: The Risk for Chronic Diseases

et al. 2021

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“…This is known as an early programming phenomenon, or priming of developing brain to pathological conditions due to experiencing the prenatal, intranatal, or early postnatal stress [ 4 ]. Stress response is always associated with hyperactivation of hypothalamic-pituitary-adrenal axis (HPA) and sympathetic nervous system, establishment of pro-inflammatory mechanisms, and long-lasting epigenomic changes that affect normal development of brain cells, multicellular ensembles, and neural circuits [ 4 , 5 , 6 , 7 , 8 ]. In addition, ELS results in dramatic metabolic changes leading to insulin resistance, obesity, and metabolic syndrome [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Early Life Stress and Metabolic Plasticity of Brain Cells: Impact on Neurogenesis and Angiogenesis

et al. 2021

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Early life stress (ELS) causes long-lasting changes in brain plasticity induced by the exposure to stress factors acting prenatally or in the early postnatal ontogenesis due to hyperactivation of hypothalamic-pituitary-adrenal axis and sympathetic nervous system, development of neuroinflammation, aberrant neurogenesis and angiogenesis, and significant alterations in brain metabolism that lead to neurological deficits and higher susceptibility to development of brain disorders later in the life. As a key component of complex pathogenesis, ELS-mediated changes in brain metabolism associate with development of mitochondrial dysfunction, loss of appropriate mitochondria quality control and mitochondrial dynamics, deregulation of metabolic reprogramming. These mechanisms are particularly critical for maintaining the pool and development of brain cells within neurogenic and angiogenic niches. In this review, we focus on brain mitochondria and energy metabolism related to tightly coupled neurogenic and angiogenic events in healthy and ELS-affected brain, and new opportunities to develop efficient therapeutic strategies aimed to restore brain metabolism and reduce ELS-induced impairments of brain plasticity.

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Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons

Cited by 69 publications

References 56 publications

A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies

A Glimpse Into the Sexual Dimorphisms in Major Depressive Disorder Through Epigenetic Studies

The Transition From Undernutrition to Overnutrition Under Adverse Environments and Poverty: The Risk for Chronic Diseases

Early Life Stress and Metabolic Plasticity of Brain Cells: Impact on Neurogenesis and Angiogenesis

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