Early-Life Stress Reprograms Stress-Coping Abilities in Male and Female Juvenile Rats

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.

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

Nature Communications ◽

10.1038/s41467-019-13085-6 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 12

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.

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Developmental programming of the HPA and HPG axes by early-life stress in male and female song sparrows

General and Comparative Endocrinology ◽

10.1016/j.ygcen.2013.11.014 ◽

2014 ◽

Vol 196 ◽

pp. 72-80 ◽

Cited By ~ 39

Author(s):

Kim L. Schmidt ◽

Elizabeth A. MacDougall-Shackleton ◽

Kiran K. Soma ◽

Scott A. MacDougall-Shackleton

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Developmental Programming ◽

Male And Female ◽

Female Song ◽

Song Sparrows

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Enhancement of nerve-injury-induced thermal and mechanical hypersensitivity in adult male and female mice following early life stress

Life Sciences ◽

10.1016/j.lfs.2014.11.012 ◽

2015 ◽

Vol 121 ◽

pp. 28-34 ◽

Cited By ~ 17

Author(s):

Takashi Nishinaka ◽

Kazuo Nakamoto ◽

Shogo Tokuyama

Keyword(s):

Nerve Injury ◽

Adult Male ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Male And Female ◽

Mechanical Hypersensitivity ◽

Female Mice

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

10.1101/624353 ◽

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.

Download Full-text