Reduced hippocampal neurogenesis in the GR+/− genetic mouse model of depression

Glucocorticoid receptor (GR) heterozygous mice (GR+/−) represent a valuable animal model for major depression. GR+/− mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR+/− animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR+/− genotype on neurogenesis in vivo. In a 2 × 2 design, GR+/− mice and GR+/+ littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR+/− genotype and as an effect of stress. Majority of the BrdU+ cells showed co-labeling with mature neuronal marker NeuN or astrocytic marker S100β with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR+/− mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression.

• Publication year

  2009

• Venue

  European Archives of Psychiatry and Clinical Neuroscience

• Publication date

  2009-07-31

• Fields of study

  Biology, Medicine, Psychology

• Identifiers
  DOI 10.1007/s00406-009-0036-yPMID 19644729PMCID 2847168
• 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.

• Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression.

  2009cited by this paper
• An animal model of a behavioral intervention for depression.

  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
• TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment.

  2008influential reference
• The contribution of failing adult hippocampal neurogenesis to psychiatric disorders

  2008cited by this paper
• Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior

  2008cited by this paper
• Glucocorticoid receptor transgenic mice as models for depression.

  2008cited by this paper
• Neurogenesis and depression: what animal models tell us about the link

  2007cited by this paper
• Neural stem cell proliferation is decreased in schizophrenia, but not in depression

  2006cited by this paper
• Brain‐derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment

  2006cited by this paper
• Two Genetic Rat Models of Arterial Hypertension Show Different Mechanisms by Which Adult Hippocampal Neurogenesis Is Increased

  2006cited by this paper
• Learned helplessness: validity and reliability of depressive-like states in mice.

  2005cited by this paper
• Mice with Genetically Altered Glucocorticoid Receptor Expression Show Altered Sensitivity for Stress-Induced Depressive Reactions

  2005influential reference
• Effect of treatment on serum brain–derived neurotrophic factor levels in depressed patients

  2005cited by this paper
• Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants

  2003cited by this paper
• Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli

  2003cited by this paper
• Repeated restraint stress suppresses neurogenesis and induces biphasic PSA‐NCAM expression in the adult rat dentate gyrus

  2003cited by this paper
• Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis

  2003cited by this paper
• Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis.

  2002cited by this paper
• Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus

  2000cited by this paper
• The Corticosteroid Receptor Hypothesis of Depression

  2000cited by this paper
• Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety

  1999cited by this paper
• Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress.

  1998cited by this paper
• Neurogenesis in the Dentate Gyrus of the Adult Tree Shrew Is Regulated by Psychosocial Stress and NMDA Receptor Activation

  1997cited by this paper

• MicroRNA-mediated regulation of BDNF in depressive disorder: a pathway to diagnosis and therapy

  2025cites this paper
• BMP Antagonist Gremlin 2 Regulates Hippocampal Neurogenesis and Is Associated with Seizure Susceptibility and Anxiety

  2024cites this paper
• Emerging roles of SIRT1 activator, SRT2104, in disease treatment

  2024cites this paper
• The role of microRNAs in depression

  2023cites this paper
• Glucocorticoid Receptor Down-Regulation Affects Neural Stem Cell Proliferation and Hippocampal Neurogenesis

  2023cites this paper
• BDNF and its Role in the Alcohol Abuse Initiated During Early Adolescence: Evidence from Preclinical and Clinical Studies

  2022cites this paper
• Neuromodulation and Hippocampal Neurogenesis in Depression: A Scoping Review.

  2022cites this paper
• The Investigation of the Effects of Repetitive Transcranialmagnetic Stimulation Treatment on Taste and Smell Sensations in Depressed Patients.

  2021cites this paper
• High-intensity Intermittent Training Enhances Spatial Memory and Hippocampal Neurogenesis Associated with BDNF Signaling in Rats.

  2021cites this paper
• Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

  2021cites this paper
• The Investigation of the Effects of Repetitive Transcranialmagnetic Stimulation Treatment on Taste and Smell Sensations in Depressed Patients

  2021cites this paper
• Dietary Fibers and Proteins Modulate Behavior via the Activation of Intestinal Gluconeogenesis

  2021cites this paper
• Glucocorticoid‐mediated mechanisms of hippocampal damage: Contribution of subgranular neurogenesis

  2020cites this paper
• Peripheral ProBDNF Delivered by an AAV Vector to the Muscle Triggers Depression-Like Behaviours in Mice

  2020cites this paper
• Factores neurobiológicos asociados a la adquisición de los trastornos depresivos: una revisión

  2019cites this paper
• Ketamine improved depressive‐like behaviors via hippocampal glucocorticoid receptor in chronic stress induced‐ susceptible mice

  2019cites this paper
• Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation

  2019cites this paper
• Factores neurobiológicos asociados a la adquisición de los trastornos depresivos: una revisión

  2019cites this paper
• Pharmacological properties and innovative therapeutic targets of novel compounds used to treat major depression

  2018cites this paper
• Fellutamide B Synthetic Path Intermediates with in Vitro Neuroactive Function Shows Mood-Elevating Effect in Stress-Induced Zebrafish Model

  2018cites this paper
• Impact of glucocorticoid on neurogenesis

  2017cites this paper
• Nuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis.

  2017cites this paper
• Enriched housing promotes post-stroke functional recovery through astrocytic HMGB1-IL-6-mediated angiogenesis

  2017cites this paper
• Actions of Brain-Derived Neurotrophic Factor and Glucocorticoid Stress in Neurogenesis

  2017cites this paper
• Charting the perfect storm: emerging biological interfaces between stress and stroke

  2017cites this paper
• Antidepressant responsiveness in adulthood is permanently impaired after neonatal destruction of the neurogenic pool

  2017cites this paper
• Exploring the concept of human OCT3 inhibitors as a novel class of antidepressants

  2016cites this paper
• Adult Neurogenesis and Psychiatric Disorders.

  2016cites this paper
• Cipadesin A, a bioactive ingredient of Xylocarpus granatum, produces antidepressant-like effects in adult mice.

  2016cites this paper
• Parental life events cause behavioral difference among offspring: Adult pre-gestational restraint stress reduces anxiety across generations

  2016cites this paper
• The Omega-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid (DHA) Reverses Corticosterone-Induced Changes in Cortical Neurons

  2015influential citation
• Hormetic effects by exercise on hippocampal neurogenesis with glucocorticoid signaling

  2015cites this paper
• Xylocarpin H, a Limonoid of <i>Xylocarpus granatum</i>, Produces Antidepressant-Like Activities in Mice

  2015cites this paper
• An examination of the impact of dietary lipids on behaviour and neurochemistry

  2015cites this paper
• Hippocampal neurogenesis, neurotrophic factors and depression: possible therapeutic targets?

  2015cites this paper
• Of mice and men: modelling post‐stroke depression experimentally

  2014cites this paper
• Implicación del factor de transcripción Nrf2 en trastornos depresivos

  2014cites this paper
• Adult hippocampal neurogenesis in depression: behavioral implications and regulation by the stress system.

  2014cites this paper
• Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis

  2014cites this paper
• Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats.

  2014cites this paper
• Stress, glucocorticoid receptors, and adult neurogenesis: a balance between excitation and inhibition?

  2014cites this paper
• Fresh approaches to antidepressant drug discovery

  2014cites this paper
• Glucocorticoid Receptor and FKBP5 Expression Is Altered Following Exposure to Chronic Stress: Modulation by Antidepressant Treatment

  2013cites this paper
• Brain-derived neurotrophic factor and glucocorticoids: reciprocal influence on the central nervous system.

  2013cites this paper
• Major depression: a role for hippocampal neurogenesis?

  2013cites this paper
• Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior

  2012cites this paper
• Glucocorticoid-Related Molecular Signaling Pathways Regulating Hippocampal Neurogenesis

  2012cites this paper
• Repetitive magnetic stimulation of human-derived neuron-like cells activates cAMP-CREB pathway

  2012cites this paper
• Female Early Adult Depression Results in Detrimental Impacts on the Behavioral Performance and Brain Development in Offspring

  2012cites this paper
• Glucocorticoids decrease astrocyte numbers by reducing glucocorticoid receptor expression in vitro and in vivo.

  2012cites this paper
• Psychosocial influences on the dynamics of adult hippocampal neurogenesis

  2012cites this paper
• Glutamatergic System and Mood Disorders

  2011cites this paper
• Hypericum perforatum differentially affects corticosteroid receptor-mRNA expression in human monocytic U-937 cells.

  2011cites this paper
• Mifepristone Prevents Stress-Induced Apoptosis in Newborn Neurons and Increases AMPA Receptor Expression in the Dentate Gyrus of C57/BL6 Mice

  2011cites this paper
• Finding the pathology of major depression through effects on gene interaction networks

  2011cites this paper
• Entstehung von Depression

  2011cites this paper
• 7. Stress and Adult Neurogenesis

  2011cites this paper
• The Interesting Interplay Between Interneurons and Adult Hippocampal Neurogenesis

  2011cites this paper
• Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression.

  2011cites this paper
• New strategies in the development of antidepressants: towards the modulation of neuroplasticity pathways.

  2011cites this paper
• The glucocorticoid receptor: pivot of depression and of antidepressant treatment?

  2011cites this paper
• Physical exercise alleviates debilities of normal aging and Alzheimer’s disease

  2011cites this paper
• Reduced olfactory bulb volume and olfactory sensitivity in patients with acute major depression.

  2010cites this paper
• Stress hormone regulation: biological role and translation into therapy.

  2010cites this paper