Gestational environment programs adult depression-like behavior through methylation of the calcitonin gene-related peptide gene

Early life exposure to specific environmental factors can increase risk for developing psychopathology including major depression in adulthood. However, the molecular pathways and epigenetic mechanisms that mediate the effects of early environments on adult mood remain poorly understood. We examined the effects of different gestational and rearing conditions on adult anxiety- and depression-like behavior using a combined reciprocal outcrossing and cross-fostering design in Balb/cJ (cJ) and C57BL/6J (B6) mouse strains. First filial (F1) hybrid offspring, which were gestated by B6 or cJ dams and then reared by either strain, were evaluated for behavior and whole-genome hippocampal gene expression during adulthood. Adult hybrid mice gestated by B6 dams showed increased depression-like behavior in the forced swim and sucrose preference tests, increased hippocampal expression of alpha calcitonin gene-related peptide (αCGRP) transcripts, and decreased methylation of the αCGRP promoter compared with those gestated by cJ dams. Differential expression of αCGRP in adulthood did not result from genomic imprinting, and differences between B6 and cJ mitochondrial DNA were not responsible for behavioral phenotypes observed. Finally, central administration of αCGRP to adult hybrid mice increased depression-like behavior, whereas the CGRP1 receptor antagonist CGRP8-37 reduced depression-like behavior in the forced swim test. Our findings suggest that gestational factors influence adult depression-like behavior through methylation of the αCGRP gene.

• Publication year

  2012

• Venue

  Molecular Psychiatry

• Publication date

  2012-09-18

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1038/mp.2012.136PMID 23044705PMCID 3543477
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Gestational and postpartum corticosterone exposure to the dam affects behavioral and endocrine outcome of the offspring in a sexually-dimorphic manner.

  2012cited by this paper
• The Roles of Neurotrophic Factor and Wnt Signaling in Depression

  2012cited by this paper
• Strain differences in sucrose- and fructose-conditioned flavor preferences in mice.

  2012cited by this paper
• Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

  2011cited by this paper
• Calcitonin Gene-Related Peptide in the Bed Nucleus of the Stria Terminalis Produces an Anxiety-Like Pattern of Behavior and Increases Neural Activation in Anxiety-Related Structures

  2011influential reference
• Infant maternal separation impairs adult cognitive performance in BALB/cJ mice

  2011cited by this paper
• Antidepressant response to chronic citalopram treatment in eight inbred mouse strains

  2011cited by this paper
• Using Animal Models to Disentangle the Role of Genetic, Epigenetic, and Environmental Influences on Behavioral Outcomes Associated with Maternal Anxiety and Depression

  2011cited by this paper
• Parent-of-origin allelic contributions to deiodinase-3 expression elicit localized hyperthyroid milieu in the hippocampus

  2011cited by this paper
• Hungry in the womb: what are the consequences? Lessons from the Dutch famine.

  2011cited by this paper
• Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age.

  2010cited by this paper
• Genes learn from stress: How infantile trauma programs us for depression

  2010cited by this paper
• Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment.

  2010cited by this paper
• Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats.

  2010cited by this paper
• Calcitonin gene-related peptide: an update on the biology

  2009cited by this paper
• Role of Central Calcitonin Gene-Related Peptide (CGRP) in Locomotor and Anxiety- and Depression-Like Behaviors in Two Mouse Strains Exhibiting a CGRP-Dependent Difference in Thermal Pain Sensitivity

  2009cited by this paper
• Lasting epigenetic influence of early-life adversity on the BDNF gene.

  2009cited by this paper
• Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses

  2008cited by this paper
• The long-term behavioural consequences of prenatal stress.

  2008cited by this paper
• Antenatal Maternal Anxiety is Related to HPA-Axis Dysregulation and Self-Reported Depressive Symptoms in Adolescence: A Prospective Study on the Fetal Origins of Depressed Mood

  2008cited by this paper
• Behavioral Effects of Chronic Fluoxetine in BALB/cJ Mice Do Not Require Adult Hippocampal Neurogenesis or the Serotonin 1A Receptor

  2008cited by this paper
• Elevated neuroimmune biomarkers in sweat patches and plasma of premenopausal women with major depressive disorder in remission: the POWER study.

  2008cited by this paper
• Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

  2008cited by this paper
• Antenatal Maternal Anxiety is Related to HPA-Axis Dysregulation and Self-Reported Depressive Symptoms in Adolescence: A Prospective Study on the Fetal Origins of Depressed Mood

  2008cited by this paper
• Role of neurotrophic factors in the etiology and treatment of mood disorders

  2007cited by this paper
• Epigenetic regulation in psychiatric disorders

  2007cited by this paper
• Prenatal exposure to maternal depression and cortisol influences infant temperament.

  2007cited by this paper
• Folate and long-chain polyunsaturated fatty acids in psychiatric disease.

  2006cited by this paper
• A Swedish national twin study of lifetime major depression.

  2006cited by this paper
• Maternal influences on adult stress and anxiety-like behavior in C57BL/6J and BALB/cJ mice: a cross-fostering study.

  2005cited by this paper
• Long-term effects of early-life environmental manipulations in rodents and primates: Potential animal models in depression research.

  2005cited by this paper
• Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment

  2005cited by this paper
• Stress, genes and the mechanism of programming the brain for later life.

  2005cited by this paper
• Neurobiological consequences of childhood trauma.

  2004cited by this paper
• Effects of Chronic Fluoxetine in Animal Models of Anxiety and Depression

  2004cited by this paper
• Maternal consumption of a high-meat, low-carbohydrate diet in late pregnancy: relation to adult cortisol concentrations in the offspring.

  2003cited by this paper
• Revisiting the mouse mitochondrial DNA sequence.

  2003cited by this paper
• Neuropsychopharmacology : The Fifth Generation of Progress

  2002cited by this paper
• Hippocampal changes in patients with a first episode of major depression.

  2002cited by this paper
• Calcitonin gene-related peptide and calcitonin in the CSF of patients with dementia and depression: possible disease markers.

  2002cited by this paper
• Genotype- and experience-dependent susceptibility to depressive-like responses in the forced-swimming test

  2002cited by this paper
• RISK FACTORS FOR MAJOR DEPRESSION AND BIPOLAR DISORDER

  2002influential reference
• Alterations induced by gestational stress in brain morphology and behaviour of the offspring.

  2001cited by this paper
• Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice

  2001cited by this paper
• Influence of genetic dissimilarity of mother and fetus on progesterone concentrations in pregnant mice and adaptive features of offspring.

  2001cited by this paper
• Behavioral despair in mice after prenatal stress

  2000cited by this paper
• Antidepressant-like behavioral effects mediated by 5-Hydroxytryptamine(2C) receptors.

  2000cited by this paper
• Discovery of a novel, paternally expressed ubiquitin-specific processing protease gene through comparative analysis of an imprinted region of mouse chromosome 7 and human chromosome 19q13.4.

  2000cited by this paper
• Sertraline, a selective serotonin reuptake inhibitor modulates extracellular noradrenaline in the rat frontal cortex

  1998cited by this paper
• Do early‐life events permanently alter behavioral and hormonal responses to stressors?

  1998cited by this paper
• The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse.

  1997cited by this paper
• Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.

  1997cited by this paper
• An Analysis of the Effects of Acute and Chronic Fluoxetine on Extracellular Norepinephrine in the Rat Hippocampus during Stress

  1997cited by this paper
• Behavioural effects of prenatal and postnatal undernutrition in rats.

  1996cited by this paper
• Increased Risk of Affective Disorders in Males after Second Trimester Prenatal Exposure to the Dutch Hunger Winter of 1944–45

  1995cited by this paper
• Increased concentration of calcitonin gene-related peptide in cerebrospinal fluid of depressed patients. A possible trait marker of major depressive disorder.

  1994cited by this paper
• Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites

  1984cited by this paper
• Differences in patterns of pup care in Mus musculus domesticus l-Comparisons between eleven inbred strains.

  1982cited by this paper
• American Journal of Epidemiology Original Contribution Diethylstilbestrol Exposure in Utero and Depression in Women

  year unknowncited by this paper

• Galcanezumab for the preventive treatment of episodic and chronic migraine in real life: A prospective multicenter study in Colombia and Mexico, including effects on anxiety and depression—on behalf of ASOLAC

  2026cites this paper
• DNA methylation studies in mouse models of depression: a systematic review.

  2025cites this paper
• Fremanezumab for the Treatment of Patients With Migraine and Comorbid Major Depressive Disorder

  2025cites this paper
• An Updated Bio‐Behavioral Profile of the Flinders Sensitive Line Rat: Reviewing the Findings of the Past Decade

  2025cites this paper
• CGRP as a potential mediator for the sexually dimorphic responses to traumatic brain injury

  2024cites this paper
• Prenatal and postnatal influences on behavioral development in a mouse model of preconceptional stress

  2024cites this paper
• Understanding the Biological Relationship between Migraine and Depression

  2024cites this paper
• Improvement of migraine depressive symptoms is not related to headache frequency: exploring the impact of anti-CGRP therapies

  2024cites this paper
• Hyperperfusion of bilateral amygdala in patients with chronic migraine: an arterial spin-labeled magnetic resonance imaging study

  2023cites this paper
• Anxiety and Depression: What Do We Know of Neuropeptides?

  2022cites this paper
• Neuropeptide Y, calcitonin gene-related peptide, and neurokinin A in brain regions of HAB rats correlate with anxiety-like behaviours.

  2022cites this paper
• Endogenous calcitonin gene-related peptide in cerebrospinal fluid and early quality of life and mental health after good-grade spontaneous subarachnoid hemorrhage—a feasibility series

  2020cites this paper
• Amygdala, neuropeptides, and chronic pain-related affective behaviors.

  2020cites this paper
• The impact of maternal depression and prenatal antidepressant exposure on child development : consideration of internal and external contextual factors

  2019cites this paper
• Dopamine D2 receptor overexpression in the nucleus accumbens core induces robust weight loss during scheduled fasting selectively in female mice

  2019cites this paper
• Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability

  2018cites this paper
• Reciprocal F1 Hybrids of Two Inbred Mouse Strains Reveal Parent-of-Origin and Perinatal Diet Effects on Behavior and Expression

  2018cites this paper
• CGRP in a gene–environment interaction model for depression: effects of antidepressant treatment

  2018influential citation
• Environmental perturbation of the circadian clock during pregnancy leads to transgenerational mood disorder-like behaviors in mice

  2017cites this paper
• Identification of a novel, fast acting GABAergic anti-depressant

  2017cites this paper
• Cross‐fostering: Elucidating the effects of gene × environment interactions on phenotypic development

  2017cites this paper
• Predictors of early-onset post-ischemic stroke depression: a cross-sectional study

  2017cites this paper
• Epigenetic regulation of G protein coupled receptor signaling and its implications in psychiatric disorders.

  2016cites this paper
• Maternal stress and diet may influence affective behavior and stress-response in offspring via epigenetic regulation of central peptidergic function

  2016cites this paper
• The relationship between calcitonin gene-related peptide and depression-like behavior.

  2016cites this paper
• Role of epigenetic factors in the development of mental illness throughout life.

  2016cites this paper
• Electroconvulsive therapy for depression : optimising treatment and exploring molecular mechanisms

  2016cites this paper
• Temporal lobe epilepsy: a unique window into living human brain epigenetic gene regulation.

  2015cites this paper
• Maternal high fat diet programs stress-induced behavioral disorder in adult offspring.

  2015influential citation
• Aberrant NMDA receptor DNA methylation detected by epigenome-wide analysis of hippocampus and prefrontal cortex in major depression

  2015cites this paper
• Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice

  2015cites this paper
• Time Course of Behavioral Alteration and mRNA Levels of Neurotrophic Factor Following Stress Exposure in Mouse

  2015cites this paper
• The role of calcitonin gene-related peptide in post-stroke depression in chronic mild stress-treated ischemic rats.

  2015cites this paper
• Potential targets for the development of novel antidepressants: future perspectives.

  2015cites this paper
• Effects of Dim Light at Night Exposure During Early Life on Adult Phenotype

  2014cites this paper
• Epigenetic Mechanisms of Early Adverse Experience in the Development of Depression

  2014cites this paper
• Epigenetics in Major Depressive Disorder

  2014cites this paper
• Epigenetic programing of depression during gestation

  2014influential citation
• What makes a good mother? Implication of inter-, and intrastrain strain "cross fostering" for emotional changes in mouse offspring.

  2014cites this paper
• Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

  2014cites this paper
• Epigenetics and depression: return of the repressed.

  2014cites this paper
• Methylation of Migraine-Related Genes in Different Tissues of the Rat

  2014cites this paper
• Age-associated decrease in global DNA methylation in patients with major depression

  2014cites this paper