Early life adversity across different cell- types in the brain

Warhaftig, Gal; Almeida, Dennys Ramon de Melo Fernandes; Turecki, Gustavo

doi:10.1016/j.neubiorev.2023.105113

Cited by 8 publications

(5 citation statements)

References 223 publications

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“…1,2 Exposure to early life adversity (ELA) is a well-established predictor of stress-related psychopathologies such as depression. [3][4][5][6][7] The link between ELA and aberrant cognitive behaviors in maturity is well supported by preclinical models of peri-adolescent (early-to-late adolescence) populations. 8,9 Various forms of social adversity during adolescence, including bullying, sexual and emotional abuse, household dysfunction, assault, social isolation, and other unpredictable chronic traumatic events, significantly increase neuropsychiatric outcomes in adolescents as well as in adults.…”

Section: Introductionmentioning

confidence: 98%

“…Adolescence constitutes a pivotal period for the maturation of neurocognitive processes, during which stress impacts brain development and results in an augmented vulnerability to mental disorders in later life 1,2 . Exposure to early life adversity (ELA) is a well‐established predictor of stress‐related psychopathologies such as depression 3–7 . The link between ELA and aberrant cognitive behaviors in maturity is well supported by preclinical models of peri‐adolescent (early‐to‐late adolescence) populations 8,9 .…”

Section: Introductionmentioning

confidence: 99%

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Transcutaneous auricular vagus nerve stimulation ameliorates adolescent depressive‐ and anxiety‐like behaviors via hippocampus glycolysis and inflammation response

Sun,

Ma,

et al. 2024

CNS Neurosci Ther

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BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) is a crucial neuromodulation therapy for depression, yet its molecular mechanism remains unclear. Here, we aim to unveil the underlying mechanisms of antidepression by systematically evaluating the change of gene expression in different brain regions (i.e., hippocampus, anterior cingulate cortex, and medial prefrontal cortex).MethodsThe adolescent depression rat model was established by chronic unpredictable mild stress (CUMS), followed by the taVNS treatment for 3 weeks. The open field test (OFT), forced swimming test (FST), elevated plus maze test (EPM), and new object recognition (NOR) test were used to evaluate depressive‐ and anxiety‐like behaviors. Gene expression analysis of three brain regions was conducted by RNA sequencing (RNA‐seq) and further bioinformatics methods.ResultsThe depressive‐ and anxiety‐like behaviors in CUMS‐exposed rats were manifested by decreased spontaneous locomotor activity of OFT, increased immobility time of FST, increased entries and time in the closed arms of EPM, and decreased new object index of NOR. Furthermore, CUMS exposure also led to alterations in gene expression within the hippocampus (HIP), anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC), suggesting a potential link between adolescent stress and pathological changes within these brain regions. TaVNS could significantly ameliorate depressive‐ and anxiety‐like behaviors. Its effects on these three brain regions were found related to regulation of the metabolism, and there were some brain region‐specific findings. Compared with ACC and mPFC, taVNS has a more concrete effect on HIP by regulating the inflammation response and glycolysis.ConclusiontaVNS is capable of ameliorating adolescent depressive‐ and anxiety‐like behaviors by regulating plenty of genes in the three brain regions. Suppressed level of inflammatory response and enhanced glycolysis manifests the dominant role of taVNS in HIP, which provides a theoretical foundation and data support for the molecular mechanism of antidepression by taVNS.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Transcutaneous auricular vagus nerve stimulation ameliorates adolescent depressive‐ and anxiety‐like behaviors via hippocampus glycolysis and inflammation response

Sun,

Ma,

et al. 2024

CNS Neurosci Ther

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“…To understand the mechanisms underlying the lasting effects of pubertal stress, our focus has been on the paraventricular nucleus of the hypothalamus (PVN), both a key brain region that regulates the hypothalamic-pituitary-adrenal (HPA) stress axis response and a region we have previously identified to have disruption of both the epigenome and transcriptome following pubertal stress (9,11). It has been of great interest to scientists and clinicians to understand the molecular underpinnings of the lasting effects of exposure to stress or trauma early in life (13)(14)(15). Here, we leveraged our pubertal stress-associated molecular signature, where six immediate early genes (IEGs) were permissively expressed at baseline in the PVN of pregnant females, to provide insight into whether early life stress-induced molecular changes are present as an immediate consequence of pubertal stress or are apparent only in adulthood.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The impact of pubertal stress and adult hormone exposure on the transcriptome of the developing hypothalamus

Gautier,

Higley,

Mendoza

et al. 2023

Preprint

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Why individuals have negative consequences following stress is a complex phenomenon that is dictated by individual factors, the timing of stress within the lifespan, and when the consequences are measured. Women who undergo adverse childhood experiences are at risk for lasting biological consequences, including affective and stress dysregulation. We have shown that pubertal adversity is associated with a blunted glucocorticoid response within the hypothalamic-pituitary-adrenal axis in both peripartum humans and mice. In mice, we examined puberty-stress reprogramming in the paraventricular nucleus (PVN) of the hypothalamus, which initiates the HPA axis response. We found that pubertal stress led to an upregulation of six immediate early genes (IEGs) in the PVN of adult, pregnant mice. Separately, we showed that the pregnancy-associated hormone allopregnanolone is necessary and sufficient to produce the blunted stress response phenotype in pubertally stressed mice. Here, we examined the response of the IEGs in the PVN to the primary disruption of pubertal stress in early adolescence and to the secondary disruption of increased allopregnanolone in pregnancy. We found that in adult female, but not male, mice previously stressed during puberty, intra-PVN allopregnanolone was sufficient to recapitulate the pubertal stress associated baseline IEG expression profile. We also examined baseline IEG expression during adolescence, where we found that IEGs have sex-specific developmental trajectories that were disrupted by pubertal stress. Altogether, these data establish that IEGs can act as a key molecular switch that leads to increased vulnerability to negative outcomes in adult, pubertally stressed animals. Understanding how the factors that produce vulnerability combine throughout the lifespan will further our understanding of the etiology of negative outcomes and will help guide both the nature and timing of potential treatments.

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“…In addition to studying how ELAs associate with changes in physiology and behavior ( 18 ), work has been conducted on ELA-associated alterations in brain circuitry and connectivity ( 18 , 19 ), cellular architecture ( 20 , 21 ), and gene expression ( 22 ). Stemming from the finding of hypothalamic-pituitary-adrenal (HPA) axis variations associated with some models of ELAs, numerous studies focused on specific glucocorticoid receptor signaling genes ( 23 ), while a smaller proportion of investigations addressed at a genome-wide level the enrichments, biological pathways, and transcriptional ( 24 ) patterns that are associated with different types of ELAs.…”

Section: Introductionmentioning

confidence: 99%

Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride

Battaglia,

Rossignol,

Lorenzo

et al. 2023

Sci. Adv.

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Early-life adversities are associated with altered defensive responses. Here, we demonstrate that the repeated cross-fostering (RCF) paradigm of early maternal separation is associated with enhancements of distinct homeostatic reactions: hyperventilation in response to hypercapnia and nociceptive sensitivity, among the first generation of RCF-exposed animals, as well as among two successive generations of their normally reared offspring, through matrilineal transmission. Parallel enhancements of acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 messenger RNA transcripts were detected transgenerationally in central neurons, in the medulla oblongata, and in periaqueductal gray matter of RCF-lineage animals. A single, nebulized dose of the ASIC-antagonist amiloride renormalized respiratory and nociceptive responsiveness across the entire RCF lineage. These findings reveal how, following an early-life adversity, a biological memory reducible to a molecular sensor unfolds, shaping adaptation mechanisms over three generations. Our findings are entwined with multiple correlates of human anxiety and pain conditions and suggest nebulized amiloride as a therapeutic avenue.

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Early life adversity across different cell- types in the brain

Cited by 8 publications

References 223 publications

Transcutaneous auricular vagus nerve stimulation ameliorates adolescent depressive‐ and anxiety‐like behaviors via hippocampus glycolysis and inflammation response

Transcutaneous auricular vagus nerve stimulation ameliorates adolescent depressive‐ and anxiety‐like behaviors via hippocampus glycolysis and inflammation response

The impact of pubertal stress and adult hormone exposure on the transcriptome of the developing hypothalamus

Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride

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