ArticlePsychoneuroendocrinology2018
Inability to suppress the stress-induced activation of the HPA axis during the peripartum period engenders deficits in postpartum behaviors in mice.
Article in Psychoneuroendocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 102 citations in OpenAlex.
- Effect of Zuranolone vs Placebo in Postpartum Depression: A Randomized Clinical Trial.JAMA psychiatry · 2021Trial
- Stress and HPA axis dysfunction impact diverse epilepsy outcomes including psychiatric comorbidities and SUDEP.Epilepsy research · 2026Review
- Adaptation of hypothalamic CRH neuron responses to stress and pup cues during motherhood.Communications biology · 2026Article
- Adolescent binge drinking causes sex-specific deficits in behavioral reactivity, endocrine recovery from stress and altered expression of hypothalamic KCC2 in males.Psychopharmacology · 2026Article
- Prenatal exposure to heat stress and postpartum depressive symptoms in the MADRES cohort in urban Los Angeles.Environmental research · 2026Article
- Appetitive maternal behavior in mice is resistant to perinatal chronic variable stress and perinatal chronic corticosterone treatment.Hormones and behavior · 2026Article
- Psychedelic therapy and postpartum depression: priorities and prospects.Therapeutic advances in psychopharmacology · 2026Review
- Uncovering the role of c-Fos in the bidirectional relationship between depression/anxiety behaviors and α-synuclein propagation in Parkinson's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- The paraventricular nucleus of the hypothalamus: a key node in the control of behavioural states.The Journal of physiology · 2025Review
- Neuroinflammation-A Crucial Factor in the Pathophysiology of Depression-A Comprehensive Review.Biomolecules · 2025Review
- Early life stress influences epilepsy outcomes in mice.Epilepsy & behavior : E&B · 2025Article
- Social isolation during pregnancy disrupts maternal behavior and hippocampal neurochemistry in rats: A role for BDNF, corticosterone, and GABAARα1.Comprehensive psychoneuroendocrinology · 2025Article
- Insulin activates parasympathetic hepatic-related neurons of the paraventricular nucleus of the hypothalamus through mTOR signaling.Journal of neurophysiology · 2025Article
- Article
- KCC2 inhibition and neuronal hyperexcitability promote extrinsic apoptosis dependent upon C1q.Frontiers in molecular neuroscience · 2025Article
- Current Developments in the Treatment of Postpartum Depression: Zuranolone.The Eurasian journal of medicine · 2024Article
- Experience-dependent information routing through the basolateral amygdala shapes behavioral outcomes.Cell reports · 2024Article
- Hypothalamic-Pituitary-Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner.eNeuro · 2024Article
- Influencing factors for postpartum depression in women with gestational diabetes mellitus.Frontiers in endocrinology · 2024Article
- Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis is normally suppressed during pregnancy. Dysregulation of the HPA axis has been proposed to play a role in postpartum depression. However, direct investigation into the relationship between the HPA axis and postpartum depression has been hindered by the lack of useful animal models. Building on our discovery of a role for the K+/Cl-co-transporter, KCC2, in the GABAergic regulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN), critical for mounting the body's physiological response to stress, we assessed the role of KCC2 in the regulation of the HPA axis during pregnancy and the postpartum period. Here we demonstrate that the normal suppression of the stress-induced activation of the HPA axis during the peripartum period involves maintenance of KCC2 in the PVN. Mice lacking KCC2 specifically in corticosterone-releasing hormone (CRH) neurons, which govern the activity of the HPA axis (KCC2/Crh mice), exhibit dysregulation of the HPA axis and abnormal postpartum behaviors. Loss of KCC2 specifically in CRH neurons in the PVN is sufficient to reproduce the depression-like phenotype and deficits in maternal behaviors during the postpartum period. Similarly, chemogenetic activation of CRH neurons in the PVN is sufficient to induce abnormal postpartum behaviors and chemogenetic silencing of CRH neurons in the PVN can ameliorate abnormal postpartum behaviors observed in KCC2/Crh mice. This study demonstrates that dysregulation of the HPA axis is sufficient to induce abnormal postpartum behaviors and deficits in maternal behaviors in mice, providing empirical support for a role of HPA axis dysfunction in the pathophysiology of postpartum depression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.