Regional Differences in Brain-Derived Neurotrophic Factor Levels and Dendritic Spine Density Confer Resilience to Inescapable Stress

Background: In the learned helplessness (LH) paradigm, approximately 35% of rats are resilient to inescapable stress. Methods: The roles of brain-derived neurotrophic factor (BDNF) and dendritic spine density in the brain regions of LH (susceptible) and non-LH rats (resilient) were examined. Western blot analysis and Golgi staining were performed. Results: BDNF levels in the medial prefrontal cortex, CA3, and dentate gyrus (DG) were significantly lower in the LH group than in the control and non-LH groups, whereas BDNF levels in the nucleus accumbens (NAc) in the LH group but not the non-LH group were significantly higher than those in the control group. Furthermore, spine density in the prelimbic cortex, CA3, and DG was significantly lower in the LH group than in the control and non-LH groups, although spine density in the NAc was significantly higher in the LH group than in the control and non-LH groups. Conclusions: The results suggest that regional differences in BDNF levels and spine density in rat brain may contribute to resilience to inescapable stress.

• Publication year

  2015

• Venue

  International Journal of Neuropsychopharmacology

• Publication date

  2015-03-04

• Fields of study

  Biology, Medicine, Psychology

• Identifiers
  DOI 10.1093/ijnp/pyu121PMID 25568287PMCID 4540100
• 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.

• Antidepressant Effects of TrkB Ligands on Depression-Like Behavior and Dendritic Changes in Mice After Inflammation

  2015cited by this paper
• Mice with altered BDNF signaling as models for mood disorders and antidepressant effects

  2014influential reference
• Differential levels of brain amino acids in rat models presenting learned helplessness or non-learned helplessness

  2013cited by this paper
• Sigma-1 receptor chaperone and brain-derived neurotrophic factor: emerging links between cardiovascular disease and depression.

  2013cited by this paper
• A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists

  2012influential reference
• The neurobiology of depression.

  2012influential reference
• Resilience to Chronic Stress Is Mediated by Hippocampal Brain-Derived Neurotrophic Factor

  2011cited by this paper
• Infusions of allopregnanolone into the hippocampus and amygdala, but not into the nucleus accumbens and medial prefrontal cortex, produce antidepressant effects on the learned helplessness rats

  2011cited by this paper
• Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure.

  2011cited by this paper
• Effect of brain‐derived neurotrophic factor haploinsufficiency on stress‐induced remodeling of hippocampal neurons

  2011cited by this paper
• Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress.

  2011cited by this paper
• Brain‐derived neurotrophic factor as a biomarker for mood disorders: An historical overview and future directions

  2010cited by this paper
• Psychobiology and molecular genetics of resilience

  2009cited by this paper
• Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines

  2008cited by this paper
• Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions.

  2007cited by this paper
• Physiology and neurobiology of stress and adaptation: central role of the brain.

  2007cited by this paper
• The mesolimbic dopamine reward circuit in depression.

  2006cited by this paper
• A neurotrophic model for stress-related mood disorders.

  2006influential reference
• Neurochemistry of the nucleus accumbens and its relevance to depression and antidepressant action in rodents.

  2006cited by this paper
• Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs.

  2005cited by this paper
• Critical role of brain-derived neurotrophic factor in mood disorders.

  2004cited by this paper
• Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats

  2003cited by this paper
• Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects.

  2003cited by this paper
• Neurobiology of depression.

  2002cited by this paper
• Brain-Derived Neurotrophic Factor Produces Antidepressant Effects in Behavioral Models of Depression

  2002cited by this paper
• The Rat Brain in Stereotaxic Coordinates

  1983cited by this paper
• The Rat Brain in Stereotaxic Coordinates

  1983cited by this paper

• Brain-derived neurotrophic factor levels after low-intensity intradialytic cycling aerobic exercise in patients on continuous hemodialysis

  2025cites this paper
• Phytochemicals Targeting BDNF Signaling for Treating Neurological Disorders

  2025cites this paper
• Sex differences in resilience at puberty depend upon divergent effects of a stress steroid at α4βδ GABAA receptors.

  2025cites this paper
• Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.

  2025cites this paper
• BDNF/CREB signaling pathway contribution in depression pathogenesis: A survey on the non-pharmacological therapeutic opportunities for gut microbiota dysbiosis.

  2024cites this paper
• Early protein restriction in rats induces anhedonia in adult offspring: a key role of BDNF-TrkB signaling in the nucleus accumbens shell.

  2024cites this paper
• Maladaptation of dentate gyrus mossy cells mediates contextual discrimination deficit after traumatic stress.

  2024cites this paper
• Influence of gut microbiota on resilience and its possible mechanisms

  2023influential citation
• The Regulation of Glutamate Transporter 1 in the Rapid Antidepressant-Like Effect of Ketamine in Mice

  2022cites this paper
• Aberrant ventral dentate gyrus structure and function in trauma susceptible mice

  2022cites this paper
• Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience

  2022cites this paper
• The hippocampus in stress susceptibility and resilience: Reviewing molecular and functional markers.

  2022cites this paper
• The role of MeCP2 and the BDNF/TrkB signaling pathway in the stress resilience of mice subjected to CSDS

  2022cites this paper
• Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex.

  2022cites this paper
• Brain Research Bulletin: Special Issue: Brain-body communication in health and diseases, Brain-gut-microbiota axis in depression: A historical overview and future directions.

  2022cites this paper
• Intranasal administration of transforming growth factor-β1 elicits rapid-acting antidepressant-like effects in a chronic social defeat stress model: A role of TrkB signaling.

  2021cites this paper
• How Stress Physically Re-shapes the Brain: Impact on Brain Cell Shapes, Numbers and Connections in Psychiatric Disorders.

  2021cites this paper
• Post-Weaning Social Isolation Causes Sex-specific Alterations to Dendritic Spine Density in Subregions of the Prefrontal Cortex and Nucleus Accumbens of Adult Mice.

  2021cites this paper
• Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule, Affecting the TrkB Signaling

  2021cites this paper
• Prenatal cyanuric acid exposure depresses hippocampal synaptic plasticity and induces spatial learning and memory deficits.

  2021cites this paper
• Requirements of Postnatal proBDNF in the Hippocampus for Spatial Memory Consolidation and Neural Function

  2021cites this paper
• mGlu2/3 receptor in the prelimbic cortex is implicated in stress resilience and vulnerability in mice.

  2021cites this paper
• Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents

  2021cites this paper
• Nicotine induces resilience to chronic social defeat stress in a mouse model of water pipe tobacco exposure by activating BDNF signaling.

  2020cites this paper
• Sulforaphane Activates Brain-Derived Neurotrophic Factor (BDNF) Transcription by NF-E2-Related factor-2 (Nrf2), Showing Prevention Effects on the Microglial of Stressed Mice

  2020cites this paper
• Diabetes mellitus, cognitive deficits and serum BDNF levels in chronic patients with schizophrenia: A case-control study.

  2020cites this paper
• Rapid-acting and long-lasting antidepressant-like action of (R)-ketamine in Nrf2 knock-out mice: a role of TrkB signaling

  2020cites this paper
• Aberrant ventral dentate gyrus structure and function in individuals susceptible to post-traumatic stress disorder

  2020cites this paper
• Severe childhood and adulthood stress associates with neocortical layer-specific reductions of mature spines in psychiatric disorders

  2020cites this paper
• Dendritic Spines: Mediators of Cognitive Resilience in Aging and Alzheimer’s Disease

  2020cites this paper
• New insights on brain‐derived neurotrophic factor epigenetics: from depression to memory extinction

  2020cites this paper
• Neuron Terminal Monoamines Related to Resilience, Depression-Like, or Non-Depression-Like Behavioral States in Learned Helplessness Paradigm.

  2020cites this paper
• The alterations of glutamate transporter 1 and glutamine synthetase in the rat brain of a learned helplessness model of depression

  2020cites this paper
• Ketamine's Dose Related Multiple Mechanisms of Actions: Dissociative Anesthetic to Rapid Antidepressant.

  2020cites this paper
• Ketamine Alleviates Postoperative Depression-Like Symptoms in Susceptible Mice: The Role of BDNF-TrkB Signaling

  2020cites this paper
• Biomarkers of resilience and susceptibility in rodent models of stress

  2020cites this paper
• The molecular and cellular mechanisms of depression: a focus on reward circuitry

  2019cites this paper
• Lack of rapid antidepressant effects of Kir4.1 channel inhibitors in a chronic social defeat stress model: Comparison with (R)‐ketamine

  2019cites this paper
• Increased BDNF‐TrkB signaling in the nucleus accumbens plays a role in the risk for psychosis after cannabis exposure during adolescence

  2019cites this paper
• Modulation of neuroplasticity‐related targets following stress‐induced acute escape deficit

  2019cites this paper
• Sex-Dependent Ketamine Addiction-Like Behavior Profile Following Exposure to Chronic Mild Stress

  2019cites this paper
• The Neurotrophic Hypothesis of Depression Revisited: New Insights and Therapeutic Implications

  2019cites this paper
• A study of limbic brain derived neurotrophic factor gene expression in male Sprague-Dawley rats trained on a learned helplessness task.

  2019cites this paper
• Abnormal composition of gut microbiota is associated with resilience versus susceptibility to inescapable electric stress

  2019cites this paper
• A potential role for microglia in stress- and drug-induced plasticity in the nucleus accumbens: A mechanism for stress-induced vulnerability to substance use disorder.

  2019cites this paper
• The Role of Brain-Derived Neurotrophic Factor in Mediating the Action of Antidepressants in the Treatment of Depression

  2019cites this paper
• Modelling resilience in adolescence and adversity: a novel framework to inform research and practice

  2019cites this paper
• Examining the Effects of Exercise on Frustration-Induced Anxiety-Like Behavior in Rats

  2019cites this paper
• Subjective arousal and perceived control clarify heterogeneity in inflammatory and affective outcomes

  2019cites this paper
• A study of brain-derived neurotrophic factor in Sprague-Dawley rats trained on a learned helplessness procedure.

  2018influential citation
• Role of TrkB-signaling in taste development and function.

  2018cites this paper
• Downregulation of Egr-1 Expression Level via GluN2B Underlies the Antidepressant Effects of Ketamine in a Chronic Unpredictable Stress Animal Model of Depression.

  2018cites this paper
• Brain-derived neurotrophic factor-TrkB signaling in the medial prefrontal cortex plays a role in the anhedonia-like phenotype after spared nerve injury

  2018cites this paper
• The facilitating effect of unfavorable lactation on the potentiation of electrocorticogram after spreading depression in awake and anesthetized adult rats

  2018cites this paper
• Keap1–Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress

  2018cites this paper
• Differential expression of serum biomarkers in hemodialysis patients with mild cognitive decline: A prospective single-center cohort study

  2018cites this paper
• Longitudinal in vivo Diffusion Tensor Imaging Detects Differential Microstructural Alterations in the Hippocampus of Chronic Social Defeat Stress-Susceptible and Resilient Mice

  2018cites this paper
• PGC-1α–FNDC5–BDNF signaling pathway in skeletal muscle confers resilience to stress in mice subjected to chronic social defeat

  2018cites this paper
• Comparison of rapid and long‐lasting antidepressant effects of negative modulators of &agr;5‐containing GABAA receptors and (R)‐ketamine in a chronic social defeat stress model

  2018cites this paper
• Essential Role of Keap1-Nrf2 Signaling in Mood Disorders: Overview and Future Perspective

  2018cites this paper
• Sustained antidepressant action of the N-methyl-D-aspartate receptor antagonist MK-801 in a chronic unpredictable mild stress model.

  2018cites this paper
• Deletion of serine racemase confers D‐serine –dependent resilience to chronic social defeat stress

  2018cites this paper
• Microglia Polarization and Endoplasmic Reticulum Stress in Chronic Social Defeat Stress Induced Depression Mouse

  2018cites this paper
• Dopamine System Dysregulation in Major Depressive Disorders

  2017cites this paper
• Blockade of interleukin-6 receptor in the periphery promotes rapid and sustained antidepressant actions: a possible role of gut–microbiota–brain axis

  2017cites this paper
• Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine

  2017cites this paper
• The Endocannabinoid, 2-arachidonoylglycerol, Regulates Resilience to Stress-induced Anxiety

  2017cites this paper
• Allostatic load and reduced cortical thickness in schizophrenia.

  2017cites this paper
• Individual differences in stress susceptibility and stress inhibitory mechanisms

  2017cites this paper
• Effects of a single bilateral infusion of R-ketamine in the rat brain regions of a learned helplessness model of depression

  2017cites this paper
• Regional differences in dendritic spine density confer resilience to chronic social defeat stress

  2017cites this paper
• Bifidobacterium in the gut microbiota confer resilience to chronic social defeat stress in mice

  2017cites this paper
• Resolving the contributions of anaesthesia, surgery, and nerve injury on brain derived neurotrophic factor expression in the medial prefrontal cortex of male rats in the CCI model of neuropathic pain

  2017cites this paper
• Rapid Antidepressant Activity of Ketamine Beyond NMDA Receptor

  2017cites this paper
• What Are the Causes for Discrepancies of Antidepressant Actions of (2R,6R)-Hydroxynorketamine?

  2017cites this paper
• Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain–liver axis

  2017cites this paper
• Development of a Novel Method to Assess the Effects of Predictability and Chronic Stress on Neuronal Morphology and Decision-Making in Rats

  2017cites this paper
• Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype

  2017cites this paper
• Antidepressant effects of combination of brexpiprazole and fluoxetine on depression-like behavior and dendritic changes in mice after inflammation

  2016cites this paper
• The correlation between perceived social support, cortisol and brain derived neurotrophic factor levels in healthy women.

  2016cites this paper
• Regulation of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain by serotonin

  2016cites this paper
• Role of Keap1-Nrf2 signaling in depression and dietary intake of glucoraphanin confers stress resilience in mice

  2016cites this paper
• Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience

  2016cites this paper
• Adjunctive treatment of brexpiprazole with fluoxetine shows a rapid antidepressant effect in social defeat stress model: Role of BDNF-TrkB signaling

  2016cites this paper
• Serum n-3 polyunsaturated fatty acids and psychological distress in early pregnancy: Adjunct Study of Japan Environment and Children's Study

  2016cites this paper
• Development of surgical skills and performance

  2016cites this paper
• Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress

  2016cites this paper
• Regulation of glutamate transporter 1 via BDNF-TrkB signaling plays a role in the anti-apoptotic and antidepressant effects of ketamine in chronic unpredictable stress model of depression

  2016cites this paper
• The interactive effects of ketamine and magnesium upon depressive-like pathology

  2016cites this paper
• Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets

  2016cites this paper
• Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression

  2016influential citation
• A role for CRH and HPA Activation in the Regulation of Plasticity Signaling, Neuroinflammation and Emotional/Mnesic Behavior Following Global Cerebral Ischemia in Rats

  2016cites this paper
• Depression-like phenotype by deletion of α7 nicotinic acetylcholine receptor: Role of BDNF-TrkB in nucleus accumbens

  2016cites this paper
• Rapid and Sustained Antidepressant Action of the mGlu2/3 Receptor Antagonist MGS0039 in the Social Defeat Stress Model: Comparison with Ketamine

  2016cites this paper
• Epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression.

  2016cites this paper
• Peripheral interleukin-6 promotes resilience versus susceptibility to inescapable electric stress

  2015cites this paper
• Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood

  2015cites this paper
• R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

  2015cites this paper
• Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist.

  2015cites this paper
• Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression

  2015influential citation