Epigenetic Regulation of the Social Brain

Bludau, Anna; Royer, Melanie; Meister, Gunter; Neumann, Inga D.; Menon, Rohit

doi:10.1016/j.tins.2019.04.001

Cited by 44 publications

(32 citation statements)

References 123 publications

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“…Previous studies have indicated that variations in parenting behaviors are associated with the differential expression of genes that regulate behavioral and endocrine responses to stress [ 88 ]. As one of the neural bases of these permanently altered gene expression patterns induced by early-life adverse environments, epigenetic mechanisms (e.g., DNA methylation) affecting the chromatin structure, post-translational modifications of histones, and non-coding RNAs are advocated [ 89 , 90 , 91 , 92 , 93 ]. Meaney is a pioneer in the research of experience-dependent chromatin plasticity in association with maternal care.…”

Section: Gene Expression Alterations Induced By Msmentioning

confidence: 99%

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

Nishi

2020

IJMS

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Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

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Section: Gene Expression Alterations Induced By Msmentioning

confidence: 99%

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

Nishi

2020

IJMS

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“…Such transgenic models range from full knockout or knock‐in of single or multiple genes to brain region‐ and gene‐specific inhibition or activation as a result of targeted modifications, eg, optogenetics or DREADD (designer receptor exclusively activated by designer drug). Furthermore, the role of epigenetics in social behaviour, as well as the effects of targeted manipulations, has been increasingly studied from the mid‐2000s onwards, providing us with insights into the behavioural effects of stressful or traumatic events, which even persists into the next generations . Therefore, studying social behaviour and especially its neurobiological basis in rodent animal models profits from the emerging new techniques in the field.…”

Section: Laboratory Rodentsmentioning

confidence: 99%

Social creatures: Model animal systems for studying the neuroendocrine mechanisms of social behaviour

Robinson

Bosch

Levkowitz

et al. 2019

J Neuroendocrinology

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The interaction of animals with conspecifics, termed social behaviour, has a major impact on the survival of many vertebrate species. Neuropeptide hormones modulate the underlying physiology that governs social interactions, and many findings concerning the neuroendocrine mechanisms of social behaviours have been extrapolated from animal models to humans. Neurones expressing neuropeptides show similar distribution patterns within the hypothalamic nucleus, even when evolutionarily distant species are compared. During evolution, hypothalamic neuropeptides and releasing hormones have retained not only their structures, but also their biological functions, including their effects on behaviour. Here, we review the current understanding of the mechanisms of social behaviours in several classes of animals, such as worms, insects and fish, as well as laboratory, wild and domesticated mammals.

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“…Concurring evidence suggests the importance of post-translational acetylation of N-terminal tails of histone residues in consolidation and maintenance of fear memory [10]. Histone deacetylases (HDACs), which catalyse the removal of acetyl groups from these N-terminal tails of histones, are key regulators of gene expression and have been found to alter social behaviour [11] as well as learning and memory [12]. Several isoforms of HDACs are found in rodents and humans, and they show remarkable brain region and task-dependent functional specificity [13].…”

Section: Introductionmentioning

confidence: 99%

Septal HDAC1 facilitates long-lasting extinction of social fear in male mice

Bludau

Paul

Neumann

et al. 2020

Preprint

Self Cite

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Social anxiety disorder (SAD) is primarily caused by traumatic social events and is characterized by intense fear and avoidance of socially enriched contexts. Formation of such intense social aversion requires learning of the association between trauma and originally neutral social stimuli. Acetylation of histones in response to learning is critical for long-term memory formation. Class I histone deacetylases (HDACs) have emerged as powerful negative regulators of long-term memory formation. However, the lack of clarity in isoform and spatial specificity in HDAC function exists. Utilizing the social fear conditioning (SFC) as well as cued fear conditioning (CFC) paradigms, we aimed to functionally characterize the role of class I HDACs, especially HDAC1, in the regulation of aversive memories in social versus non-social contexts. Using cFos expression as a marker of cellular activity, we revealed that the lateral septum (LS) was specifically activated post-acquisition in socially fear conditioned (SFC+) mice. We further measured an increase in activity-inducing HDAC1 phosphorylation at serine residues within the septum of SFC+ mice during extinction of social fear. Pharmacological inhibition of HDAC1 within the LS facilitated, while viral overexpression of septal HDAC1 impaired extinction of social fear. Finally, we found that the abovementioned facilitation of extinction memory by HDAC1 inhibition was long-lasting and persists even after 30 days of extinction. Our results show that LS-HDAC1 is a key regulator of long-lasting social fear extinction, which points towards HDAC1 as a potential therapeutic target for SAD.

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Epigenetic Regulation of the Social Brain

Cited by 44 publications

References 123 publications

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

Social creatures: Model animal systems for studying the neuroendocrine mechanisms of social behaviour

Septal HDAC1 facilitates long-lasting extinction of social fear in male mice

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