Neurodevelopmental plasticity and psychiatric vulnerability

2015 ◽  
Vol 30 (S2) ◽  
pp. S70-S70
Author(s):  
A. Dayer
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Methylation Status ◽  
Early Life Stress ◽  
Childhood Adversity ◽  
Cellular Level ◽  
Special Focus ◽  
Serotonin System ◽  
Increase Risk

The early developmental period is characterized by a high degree of plasticity and, consequently, is very sensitive to environmental factors, such as early life stressors (ELS). Exposure to ELS is known to increase risk to psychopathologies such as depression and anxiety disorders later in life . At a cellular level, alterations in the migration and integration of GABAergic interneurons (INs) in cortical circuits have emerged as a key processes involved in the vulnerability to psychiatric disorders . In humans and rodents, ELS interacts with genes regulating the serotonin system to increase risk to stress-related disorders . In addition, ELS is associated to a variety of epigenetic methylation changes in blood DNA from patients displaying a high loading of ELS . Here, we aimed to investigate the role of the ionotropic serotonin 3A receptor (5-HT3AR) at a genetic and epigenetic level in rodent and human models of early-life stress. We will first present data indicating that the 5-HT3AR is specifically expressed in a subset of cortical INs derived from the caudal ganglionic eminence (CGE) and controls early steps of cortical circuit assembly . Interestingly, the migration, transcriptional programs and positioning of 5-HT3AR expressing interneuron subtypes were found to be dysregulated in pathological models of early-life serotonin dysregulation. At a behavioral level, we found that ELS interacts with the 5-HTR3A to modulate social behaviors. Finally, we will present human data indicating that childhood adversity significantly impacts the methylation status of the promoter region of the human 5-HT3AR in an allele-specific manner. Taken together, this presentation will highlight the importance of the serotonin system in early life development and psychopathology with a special focus on the role of the 5-HT3AR in cortical interneuron development.

scholarly journals Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine
Keyword(s):  
Glucocorticoid Receptor ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Glucocorticoid Receptors ◽  
Early Life Stress ◽  
Nociceptive Threshold ◽  
Male And Female ◽  
Mechanical Nociceptive Threshold

Fibromyalgia and other chronic musculoskeletal pain syndromes are associated with stressful early life events, which can produce a persistent dysregulation in the hypothalamic-pituitary adrenal (HPA) stress axis function, associated with elevated plasm levels of corticosterone in adults. To determine the contribution of the HPA axis to persistent muscle hyperalgesia in adult rats that had experienced neonatal limited bedding (NLB), a form of early-life stress, we evaluated the role of glucocorticoid receptors on muscle nociceptors in adult NLB rats. In adult male and female NLB rats, mechanical nociceptive threshold in skeletal muscle was significantly lower than in adult control (neonatal standard bedding) rats. Furthermore, adult males and females that received exogenous corticosterone (via dams’ milk) during postnatal days 2–9, displayed a similar lowered mechanical nociceptive threshold. To test the hypothesis that persistent glucocorticoid receptor signaling in the adult contributes to muscle hyperalgesia in NLB rats, nociceptor expression of glucocorticoid receptor (GR) was attenuated by spinal intrathecal administration of an oligodeoxynucleotide (ODN) antisense to GR mRNA. In adult NLB rats, GR antisense markedly attenuated muscle hyperalgesia in males, but not in females. These findings indicate that increased corticosterone levels during a critical developmental period (postnatal days 2–9) produced by NLB stress induces chronic mechanical hyperalgesia in male and female rats that persists in adulthood, and that this chronic muscle hyperalgesia is mediated, at least in part, by persistent stimulation of glucocorticoid receptors on sensory neurons, in the adult male, but not female rat.

The Role of Early Life Stress in HPA Axis and Anxiety

2020 ◽  
pp. 141-153 ◽  
Author(s):  
Mario F. Juruena ◽  
Filip Eror ◽  
Anthony J. Cleare ◽  
Allan H. Young
Keyword(s):  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

scholarly journals A cellular defense memory imprinted by early life toxic stress

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Eszter Gecse ◽  
Beatrix Gilányi ◽  
Márton Csaba ◽  
Gábor Hajdú ◽  
Csaba Sőti
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Perinatal Period ◽  
Cellular Level ◽  
Adult Survival ◽  
Transcriptional Responses ◽  
C Elegans ◽  
Cellular Defense ◽  
Bacterial Lawn

AbstractStress exposure early in life is implicated in various behavioural and somatic diseases. Experiences during the critical perinatal period form permanent, imprinted memories promoting adult survival. Although imprinting is widely recognized to dictate behaviour, whether it actuates specific transcriptional responses at the cellular level is unknown. Here we report that in response to early life stresses, Caenorhabditis elegans nematodes form an imprinted cellular defense memory. We show that exposing newly-born worms to toxic antimycin A and paraquat, respectively, stimulates the expression of toxin-specific cytoprotective reporters. Toxin exposure also induces avoidance of the toxin-containing bacterial lawn. In contrast, adult worms do not exhibit aversive behaviour towards stress-associated bacterial sensory cues. However, the mere re-encounter with the same cues reactivates the previously induced cytoprotective reporters. Learned adult defenses require memory formation during the L1 larval stage and do not appear to confer increased protection against the toxin. Thus, exposure of C. elegans to toxic stresses in the critical period elicits adaptive behavioural and cytoprotective responses, which do not form imprinted aversive behaviour, but imprint a cytoprotective memory. Our findings identify a novel form of imprinting and suggest that imprinted molecular defenses might underlie various pathophysiological alterations related to early life stress.

scholarly journals Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Catherine Jensen Peña ◽  
Milo Smith ◽  
Aarthi Ramakrishnan ◽  
Hannah M. Cates ◽  
Rosemary C. Bagot ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Cortical Plasticity ◽  
Early Life Stress ◽  
Stress Sensitivity ◽  
Sensitive Period ◽  
Male And Female ◽  
Reward Circuitry ◽  
Female Mice ◽  
Increase Risk

Abstract Abuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain’s transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.

Cytokines during acute abstinence of crack cocaine: The role of early life stress

2015 ◽  
Vol 146 ◽  
pp. e127
Author(s):  
Rodrigo Grassi-Oliveira ◽  
Mateus L. Levandowski ◽  
Thiago W. Viola ◽  
Luiz E. Wearick ◽  
Julio Carlos Pezzi ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Crack Cocaine ◽  
Early Life Stress

Riluzole Normalizes Early-Life Stress-Induced Visceral Hypersensitivity in Rats: Role of Spinal Glutamate Reuptake Mechanisms

2010 ◽  
Vol 138 (7) ◽  
pp. 2418-2425 ◽  
Author(s):  
Romain–Daniel Gosselin ◽  
Richard M. O'Connor ◽  
Monica Tramullas ◽  
Marcela Julio–Pieper ◽  
Timothy G. Dinan ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Visceral Hypersensitivity

scholarly journals Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

2019 ◽  
Author(s):  
Catherine Jensen Peña ◽  
Milo Smith ◽  
Aarthi Ramakrishnan ◽  
Hannah M. Cates ◽  
Rosemary C. Bagot ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Cortical Plasticity ◽  
Early Life Stress ◽  
Stress Sensitivity ◽  
Sensitive Period ◽  
Male And Female ◽  
Reward Circuitry ◽  
Female Mice ◽  
Increase Risk

ABSTRACTAbuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain’s transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.

scholarly journals Hippocampal astroglial hypertrophy in mice subjected to early life maternal deprivation

2021 ◽  
Author(s):  
Arnab Nandi ◽  
Garima Virmani ◽  
Swananda Marathe
Keyword(s):  
Immune Responses ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Stratum Radiatum ◽  
Late Adulthood ◽  
Synaptic Physiology ◽  
And Behavior

Early-life stress (ELS), including chronic deprivation of maternal care, exerts persistent life-long effects on animal physiology and behavior, and is associated with several neurodevelopmental disorders. Long-lasting changes in neuronal plasticity and electrophysiology are documented extensively in the animal models of ELS. However, the role of astroglia in the lasting effects of ELS remains elusive. Astrocytes are intricately involved in the regulation of synaptic physiology and behavior. Moreover, astrocytes play a major role in the innate and adaptive immune responses in the central nervous system (CNS). The role of immune responses and neuroinflammation in the altered brain development and persistent adverse effects of ELS are beginning to be explored. Innate immune response in the CNS is characterized by a phenomenon called astrogliosis, a process in which astrocytes undergo hypertrophy, along with changes in gene expression and function. While the immune activation and neuroinflammatory changes concomitant with ELS, or in juveniles and young adults have been reported, it is unclear whether mice subjected to ELS exhibit astrogliosis-like alterations well into late-adulthood. Here, we subjected mice to maternal separation from postnatal day 2 to day 22 and performed comprehensive morphometric analysis of hippocampal astrocytes during late-adulthood. We found that the astrocytes in the stratum radiatum region of the CA1 hippocampal subfield from maternally separated mice exhibit significant hypertrophy as late as 8 months of age, revealing the crucial changes in astrocytes that manifest long after the cessation of ELS. This study highlights the persistence of neuroinflammatory changes in mice exposed to ELS.

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