The Role of Early Life Stress in HPA Axis and Anxiety

Author(s):  
Mario F. Juruena ◽  
Filip Eror ◽  
Anthony J. Cleare ◽  
Allan H. Young
2017 ◽  
pp. 71-80 ◽  
Author(s):  
Mario F. Juruena ◽  
Anthony J. Cleare ◽  
Allan H. Young

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine

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.


2020 ◽  
Vol 21 (19) ◽  
pp. 7212
Author(s):  
Mayumi Nishi

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.


2015 ◽  
Vol 30 (S2) ◽  
pp. S70-S70
Author(s):  
A. Dayer

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.


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

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

2011 ◽  
Vol 23 (4) ◽  
pp. 1039-1058 ◽  
Author(s):  
Marilyn J. Essex ◽  
Elizabeth A. Shirtcliff ◽  
Linnea R. Burk ◽  
Paula L. Ruttle ◽  
Marjorie H. Klein ◽  
...  

AbstractThe hypothalamic–pituitary–adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.


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