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

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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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.

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Effects of Early-Life Stress on Social and Anxiety-Like Behaviors in Adult Mice: Sex-Specific Effects

Behavioural Neurology ◽

10.1155/2018/1538931 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 29

Author(s):

Natalya P. Bondar ◽

Arina A. Lepeshko ◽

Vasiliy V. Reshetnikov

Keyword(s):

Social Behavior ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Individual Behavior ◽

Male And Female ◽

Female Mice ◽

Specific Effects ◽

The Social

Stressful events in an early postnatal period have critical implications for the individual’s life and can increase later risk for psychiatric disorders. The aim of this study was to investigate the influence of early-life stress on the social behavior of adult male and female mice. C57Bl/6 mice were exposed to maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal day 2 through 14. Adult male and female mice were tested for social behavior in the social interaction test and for individual behavior in the plus-maze and open-field tests. Female mice exposed to maternal separation had increased social behavior and increased anxiety. MS male mice had no changes in social behavior but had significantly disrupted individual behavior, including locomotor and exploratory activity. Handling had positive effects on social behavior in males and females and decreased anxiety in males. Our results support the hypothesis that brief separation of pups from their mothers (handling), which can be considered as moderate stress, may result in future positive changes in behavior. Maternal separation has deleterious effects on individual behavior and significant sex-specific effects on social behavior.

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Impact of mothers’ past experience and early-life stress on aggression and cognition in adult male mice

10.1101/453084 ◽

2018 ◽

Author(s):

V. Reshetnikov ◽

Yu. Ryabushkina ◽

N. Bondar

Keyword(s):

Locomotor Activity ◽

Adult Male ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Life Experience ◽

Early Life Stress ◽

Male Mice ◽

Female Mice ◽

Stressful Experience

AbstractEarly life is an important period for brain development and behavioral programming. Both reduced maternal care and stress in early life are risk factors for various psychiatric disorders. Here, we hypothesized that females’ stressful experience in their early life can lead to a disruption of mother-offspring interactions toward their own progeny. The objective of this study is to assess the effects of mothers’ past stressful experience, early-life stress alone or both on behavior in adult male mice. In this study, female mice were allowed to raise their pups either without exposure to stress (normal rearing condition, NC) or with exposure to maternal separation (3h/day, maternal separation, MS) on postnatal days 2–14. Adult F1 female mice who had experienced MS (stressed mothers, SM) or had been reared normally (undisturbed mothers, UM) were used for generating F2 offspring to be or not to be further exposed to early-life stress. We assessed anxiety-like behavior, exploratory activity, locomotor activity, aggression and cognition in four groups of adult F2 males (UM+NC, UM+MS, SM+NC, SM+MS). We found that SM+MS males become more aggressive if agonistic contact is long enough, suggesting a change in their social coping strategy. Moreover, these aggressive males tended to improve longterm spatial memory. Aggressive SM+NC males, in contrast, showed learning impairments. We did not find any significant differences in anxiety-like behavior or exploratory and locomotor activity. Overall, our findings suggest that mothers’ early-life experience may have important implications for the adult behavior of their offspring.

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Adolescent oxytocin administration reduces depression-like behaviour induced by early life stress in adult male and female rats

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2021.110279 ◽

2021 ◽

Vol 110 ◽

pp. 110279

Author(s):

Jade L. Thornton ◽

Nicholas A. Everett ◽

Paige Webb ◽

Anita J. Turner ◽

Jennifer L. Cornish ◽

...

Keyword(s):

Adult Male ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Female Rats ◽

Male And Female ◽

Male And Female Rats

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Early life stress impairs fear conditioning in adult male and female rats

Brain Research ◽

10.1016/j.brainres.2006.03.009 ◽

2006 ◽

Vol 1087 (1) ◽

pp. 142-150 ◽

Cited By ~ 91

Author(s):

Therese A. Kosten ◽

Hongjoo J. Lee ◽

Jeansok J. Kim

Keyword(s):

Fear Conditioning ◽

Adult Male ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Female Rats ◽

Male And Female ◽

Male And Female Rats

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Cocaine-Induced Impulsivity is Differentially Expressed in Male and Female Mice Exposed to Maternal Separation and is Associated with Alterations in AMPA Receptors Subunits

10.1101/2020.06.05.136812 ◽

2020 ◽

Author(s):

Adriana Castro-Zavala ◽

Ana Martin-Sanchez ◽

Larisa Montalvo-Martínez ◽

Alberto Camacho-Morales ◽

Olga Valverde

Keyword(s):

Protein Expression ◽

Ampa Receptors ◽

Life Stress ◽

Early Life ◽

Maternal Separation ◽

Early Life Stress ◽

Male Mice ◽

Male And Female ◽

Female Mice ◽

Cocaine Seeking

ABSTRACTImpulsivity is a key trait in the diagnosis of major depressive disorder (MDD) and substance use disorder (SUD). MDD is a chronic illness characterized by sadness, insomnia, and loss of interest. SUD is a chronic and relapsing disorder characterized by the consumption of drugs despite their negative consequences. Among drugs of abuse, cocaine is the most consumed psychostimulant. Animal studies demonstrated that increased impulsivity predicts predisposition to acquire cocaine self-administration (SA) behaviour with an increased cocaine-intake. Moreover, early-life stress represents a vulnerability factor to develop depressive disorders and drug addiction. Maternal separation with early weaning (MSEW) is an animal model that allows examining the impact of early-life stress on cocaine abuse. In this study, we aimed to explore changes in MSEW-induced impulsivity to determine potential associations between depression-like and cocaine-seeking behaviours in male and female mice. We also evaluated possible alterations in the AMPA receptors (AMPArs) composition and glutamatergic neurotransmission. We exposed mice to MSEW and the behavioural tests were performed during adulthood. Moreover, GluA1, GluA2 mRNA and protein expression were evaluated in the medial Prefrontal Cortex (mPFC). Results showed higher impulsive cocaine-seeking in females, independently the MSEW, as well as an increase in GluA1 and GluA2 protein expression. Moreover, MSEW induced downregulation of Gria2 and increased the GluA1/GluA2 ratio, only in male mice. In conclusion, female mice expressed higher mPFC glutamatergic function, which potentiated their impulsivity during cocaine SA. Also, data indicated that MSEW alters glutamatergic function in mPFC of male mice, increasing the glutamatergic excitability.

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