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 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.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
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.

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

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.

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.

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol

2021 ◽  
pp. 110508
Author(s):  
Ana Martín-Sánchez ◽  
Héctor González-Pardo ◽  
Laia Alegre-Zurano ◽  
Adriana Castro-Zavala ◽  
Isabel López-Taboada ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Mice ◽  
Molecular Alterations

scholarly journals Evidence for a sensitive period in the effects of early life stress on hippocampal volume

2018 ◽  
Vol 22 (3) ◽  
Author(s):  
Kathryn L. Humphreys ◽  
Lucy S. King ◽  
Matthew D. Sacchet ◽  
M. Catalina Camacho ◽  
Natalie L. Colich ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Hippocampal Volume ◽  
Sensitive Period

scholarly journals Early Life Stress Enhances the Obesogenic Response in Female Mice Via Mineralocorticoid Receptor (MR) signaling

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Jacqueline Leachman ◽  
Sundus Ghuneim ◽  
Carolina Dalmasso ◽  
Nermin Ahmed ◽  
Mei Xu ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Mineralocorticoid Receptor ◽  
Early Life Stress ◽  
Female Mice

P.220 FKBP51 loss in glutamatergic forebrain neurons and early life stress exposure shape anxiety and cognition in female mice

2020 ◽  
Vol 31 ◽  
pp. S33-S34
Author(s):  
L. Van Doeselaar ◽  
C. Engelhardt ◽  
J. Bordes ◽  
L. Brix ◽  
J. Deussing ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Stress Exposure ◽  
Female Mice ◽  
Forebrain Neurons
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