Early Life Stress Enhances Behavioral Vulnerability to Stress through the Activation of REST4-Mediated Gene Transcription in the Medial Prefrontal Cortex of Rodents

Uchida, Shinichi; Hara, Kumiko; Kobayashi, Akito; Funato, Hiromasa; Hobara, Teruyuki; Otsuki, Koji; Yamagata, Hirotaka; McEwen, Bruce S.; Watanabe, Yoshifumi

doi:10.1523/jneurosci.1436-10.2010

Cited by 260 publications

(207 citation statements)

References 65 publications

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“…À l'heure actuelle, les espèces étudiées comprennent les rongeurs, les moutons et des primates non humains. Les traitements utilisés mettent en oeuvre soit des restrictions alimentaires chez la femelle gestante (restriction protéique ou calorique globale), soit des restrictions vasculaires par ligature des artères utérines (provoquant une réduction de l'apport de nutriments au foetus), soit l'induction d'un diabète ou d'une obésité expérimentale chez la mère (évoqués ultérieurement), soit un stress provoqué par la séparation maternelle précoce chez les rongeurs qui engendre des comportements anxieux ou dépressifs chez les descendants [23]. Dans la prochaine section, nous évoquerons principalement les modèles animaux dans le contexte du diabète ou du métabolisme, les hypothèses et les mécanismes qui en découlent, et comment les approches se sont complexifiées chez les rongeurs, en nous appuyant sur un exemple concret (Figure 2).…”

Section: Le Modèle De Restriction Utéro-placentaireunclassified

Le concept des origines développementales de la santé

Munier¹,

Delpierre²,

Bréant³

2016

Med Sci (Paris)

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Section: Le Modèle De Restriction Utéro-placentaireunclassified

Le concept des origines développementales de la santé

Munier¹,

Delpierre²,

Bréant³

2016

Med Sci (Paris)

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“…Behavioral testing of adult male mice was performed during the light phase of the light/dark cycle, as previously reported (5,35,36). PEI-mediated gene transfer was performed as previously described (5,36).…”

Section: Methodsmentioning

confidence: 99%

“…It has been suggested that neuronal activity regulates a complex program of gene expression involved in structural and functional plasticity (3). Recent evidence has indicated that aberrant gene regulation in early brain development can affect brain function and subsequent affective behavior, as well as behavioral responses to stress during adulthood in rodents (4,5).…”

mentioning

confidence: 99%

Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1

Uchida

Hara

Kobayashi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Aberrant transcriptional regulation in the brain is thought to be one of the key components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Heat shock factors (HSFs) modulate cellular homeostasis through the control of gene expression. However, the roles of HSFs in brain function have yet to be elucidated fully. In the present study, we attempted to clarify the role of HSF1-mediated gene regulation in neuronal and behavioral development using HSF1-deficient (HSF1 −/− ) mice. We found granule neurons of aberrant morphology and impaired neurogenesis in the dentate gyrus of HSF1 −/− mice. In addition, HSF1 −/− mice showed aberrant affective behavior, including reduced anxiety and sociability but increased depression-like behavior and aggression. Furthermore, HSF1 deficiency enhanced behavioral vulnerability to repeated exposure to restraint stress. Importantly, rescuing the HSF1 deficiency in the neonatal but not the adult hippocampus reversed the aberrant anxiety and depression-like behaviors. These results indicate a crucial role for hippocampal HSF1 in neuronal and behavioral development. Analysis of the molecular mechanisms revealed that HSF1 directly modulates the expression of polysialyltransferase genes, which then modulate polysialic acid-neural cell adhesion molecule (PSA-NCAM) levels in the hippocampus. Enzymatic removal of PSA from the neonatal hippocampus resulted in aberrant behavior during adulthood, similar to that observed in HSF1 −/− mice. Thus, these results suggest that one role of HSF1 is to control hippocampal PSA-NCAM levels through the transcriptional regulation of polysialyltransferases, a process that might be involved in neuronal and behavioral development in mice.emotion | spine density | neuronal maturation | polysialylation T here is increasing evidence that aberrant transcriptional regulation is one of the key components of the pathogenesis and pathophysiology of neuropsychiatric disorders (1, 2). It has been suggested that neuronal activity regulates a complex program of gene expression involved in structural and functional plasticity (3). Recent evidence has indicated that aberrant gene regulation in early brain development can affect brain function and subsequent affective behavior, as well as behavioral responses to stress during adulthood in rodents (4, 5).Heat shock factors (HSFs) bind to the conserved heat shock element (HSE) consensus sequence and facilitate the transcriptional activation or repression of HSE-containing target genes (6). In mammals, the HSF family consists of four members (HSF1-4) that are considered functionally distinct. HSF1 is an essential molecule for facilitating the response to cellular stress (e.g., elevated temperature, oxidative stress, and increased protein misfolding) and also is required for developmental processes, whereas HSF2 and HSF4 are involved in cell differentiation and development (7). Among the mammalian HSFs, HSF1 is the master transactivator of heat shock proteins, which function as molecular chaperones at various...

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“…In addition, maternally supplied rest also modulates later migration of facial branchiomotor neurons (Love and Prince, 2015). An early function of REST has also been demonstrated in rodents, where maternal deprivation decreases REST levels (Uchida et al, 2010;RodenasRuano et al, 2012). Subsequent misregulation of NMDA receptor gene expression leads to changes in synaptic plasticity (Rodenas-Ruano et al, 2012).…”

Section: Introductionmentioning

confidence: 91%

Maternal Rest/Nrsf Regulates Zebrafish Behavior throughsnap25a/b

Moravec

Samuel

Weng³

et al. 2016

J. Neurosci.

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During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development. Here we show that in zebrafish, maternally supplied rest regulates expression of target genes during larval development and has lifelong impacts on behavior. Larvae deprived of maternal rest are hyperactive and show atypical spatial preferences. Adult male fish deprived of maternal rest present with atypical spatial preferences in a novel environment assay. Transcriptome sequencing revealed 158 genes that are repressed by maternal rest in blastula stage embryos. Furthermore, we found that maternal rest is required for target gene repression until at least 6 dpf. Importantly, disruption of the RE1 sites in either snap25a or snap25b resulted in behaviors that recapitulate the hyperactivity phenotype caused by absence of maternal rest. Both maternal rest mutants and snap25a RE1 site mutants have altered primary motor neuron architecture that may account for the enhanced locomotor activity. These results demonstrate that maternal rest represses snap25a/b to modulate larval behavior and that early Rest activity has lifelong behavioral impacts.

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Early Life Stress Enhances Behavioral Vulnerability to Stress through the Activation of REST4-Mediated Gene Transcription in the Medial Prefrontal Cortex of Rodents

Cited by 260 publications

References 65 publications

Le concept des origines développementales de la santé

Le concept des origines développementales de la santé

Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1

Maternal Rest/Nrsf Regulates Zebrafish Behavior throughsnap25a/b

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