Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice

Background The pathogenesis of depression is closely related to changes in hippocampal synaptic plasticity; however, the underlying mechanism is still unclear. Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), a postsynaptic scaffold protein in excitatory synapses important for synaptic plasticity, is highly expressed in the hippocampus and has been implicated in several psychiatric disorders. However, the role of BAIAP2 in depression remains poorly understood. Methods In the present study, a mouse model of depression was established via exposure to chronic mild stress (CMS). An adeno-associated virus (AAV) vector expressing BAIAP2 was injected into the hippocampal brain region of mice and a BAIAP2 overexpression plasmid was transfected into HT22 cells to upregulate BAIAP2 expression. Depression- and anxiety-like behaviors and dendritic spine density were examined in mice using behavioral tests and Golgi staining, respectively. In vitro, hippocampal HT22 cells were treated with corticosterone (CORT) to simulate the stress state, and the effect of BAIAP2 on CORT-induced cell injury was explored. Reverse transcription-quantitative PCR and western blotting were employed to determine the expression levels of BAIAP2 and those of the synaptic plasticity-related proteins glutamate receptor ionotropic, AMPA 1 (GluA1), and synapsin 1 (SYN1). Results Mice exposed to CMS exhibited depression- and anxiety-like behaviors accompanied by decreased levels of BAIAP2 in the hippocampus. In vitro, the overexpression of BAIAP2 increased the survival rate of CORT-treated HT22 cells and upregulated the expression of GluA1 and SYN1. Consistent with the in vitro data, the AAV-mediated overexpression of BAIAP2 in the hippocampus of mice significantly inhibited CMS-induced depression-like behavior, concomitant with increases in dendritic spine density and the expression of GluA1 and SYN1 in hippocampal regions. Conclusion Our findings indicate that hippocampal BAIAP2 can prevent stress-induced depression-like behavior and may be a promising target for the treatment of depression or other stress-related diseases.

[1]  C. Yook,et al.  Adult re-expression of IRSp53 rescues NMDA receptor function and social behavior in IRSp53-mutant mice , 2022, Communications Biology.

[2]  M. Gong,et al.  Hippocampal semaphorin 3B improves depression‐like behaviours in mice by upregulating synaptic plasticity and inhibiting neuronal apoptosis , 2022, Journal of neurochemistry.

[3]  Eunjoon Kim,et al.  IRSp53 promotes postsynaptic density formation and actin filament bundling , 2022, The Journal of cell biology.

[4]  Xin-hao Wang,et al.  Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors , 2022, Brain Research Bulletin.

[5]  D. Bhugra,et al.  Analysis of global prevalence of mental and substance use disorders within countries: focus on sociodemographic characteristics and income levels , 2022, International review of psychiatry.

[6]  Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 , 2022, The lancet. Psychiatry.

[7]  Eunjoon Kim,et al.  Corrigendum: IRSp53 Deletion in Glutamatergic and GABAergic Neurons and in Male and Female Mice Leads to Distinct Electrophysiological and Behavioral Phenotypes , 2021, Frontiers in Cellular Neuroscience.

[8]  Penghui Zhao,et al.  Effects of Exogenous Biliverdin Treatment on Neurobehaviors in Mice. , 2021, Biological & pharmaceutical bulletin.

[9]  Yun Shi,et al.  Sulfur dioxide derivatives produce antidepressant- and anxiolytic-like effects in mice , 2020, Neuropharmacology.

[10]  C. Tripodo,et al.  IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules , 2020, Nature Communications.

[11]  Eunjoon Kim,et al.  IRSp53 Deletion in Glutamatergic and GABAergic Neurons and in Male and Female Mice Leads to Distinct Electrophysiological and Behavioral Phenotypes , 2020, Frontiers in Cellular Neuroscience.

[12]  S. Lammel,et al.  Chronic Stress Induces Activity, Synaptic, and Transcriptional Remodeling of the Lateral Habenula Associated with Deficits in Motivated Behaviors , 2019, Neuron.

[13]  Derrick J. Phillips,et al.  Role of corticosterone in altered neurobehavioral responses to acute stress in a model of compromised hypothalamic-pituitary-adrenal axis function , 2019, Psychoneuroendocrinology.

[14]  Yiming Li,et al.  Repeated arctigenin treatment produces antidepressant- and anxiolytic-like effects in mice , 2019, Brain Research Bulletin.

[15]  Bao-Ming Li,et al.  Chronic Stress Remodels Synapses in an Amygdala Circuit–Specific Manner , 2019, Biological Psychiatry.

[16]  Fangfang Li,et al.  Brazilin Treatment Produces Antidepressant- and Anxiolytic-Like Effects in Mice. , 2019, Biological & pharmaceutical bulletin.

[17]  Seungah Lee,et al.  The protective effects of ethanolic extract of Clematis terniflora against corticosterone-induced neuronal damage via the AKT and ERK1/2 pathway , 2018, BMB reports.

[18]  Tyler W LeBaron,et al.  SuHeXiang Essential Oil Inhalation Produces Antidepressant- and Anxiolytic-Like Effects in Adult Mice. , 2018, Biological & pharmaceutical bulletin.

[19]  Karl J. Friston,et al.  A brain network model for depression: From symptom understanding to disease intervention , 2018, CNS neuroscience & therapeutics.

[20]  Z. Fu,et al.  Chronic corticosterone-induced depression mediates premature aging in rats. , 2018, Journal of affective disorders.

[21]  G. Hu,et al.  Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to chronic social defeat stress via regulating the stability of surface AMPARs , 2017, Molecular Psychiatry.

[22]  Lingjiang Li,et al.  From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder , 2017, Front. Cell. Neurosci..

[23]  C. McIntyre,et al.  Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD , 2017, Front. Pharmacol..

[24]  R. Haltiwanger,et al.  Biological functions of fucose in mammals. , 2017, Glycobiology.

[25]  Paolo Santonastaso,et al.  Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls , 2017, World psychiatry : official journal of the World Psychiatric Association.

[26]  J. Cryan,et al.  Stress and adolescent hippocampal neurogenesis: diet and exercise as cognitive modulators , 2017, Translational Psychiatry.

[27]  Chong Chen,et al.  The exercise-glucocorticoid paradox: How exercise is beneficial to cognition, mood, and the brain while increasing glucocorticoid levels , 2017, Frontiers in Neuroendocrinology.

[28]  R. Cui,et al.  The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex , 2017, Neural plasticity.

[29]  C. Y. Lim,et al.  Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development , 2017, Scientific Reports.

[30]  C. Limatola,et al.  Erratum: Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment , 2015, Molecular psychiatry.

[31]  J. Herman,et al.  Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response. , 2016, Comprehensive Physiology.

[32]  K. Roche,et al.  GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons , 2016, Nature Communications.

[33]  G. Aghajanian,et al.  Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants , 2016, Nature Medicine.

[34]  Eunjoon Kim,et al.  IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders , 2016, Neuropharmacology.

[35]  Xin-Yun Lu,et al.  Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors , 2015, The international journal of neuropsychopharmacology.

[36]  A. Khajavi,et al.  Burden of Hepatitis C in Iran Between 1990 and 2010: findings from the Global Burden of Disease Study 2010. , 2015, Archives of Iranian medicine.

[37]  X. Qin,et al.  Research on the Pathological Mechanism and Drug Treatment Mechanism of Depression , 2015, Current neuropharmacology.

[38]  M. Jung,et al.  Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression , 2015, Nature Neuroscience.

[39]  E. Banks,et al.  De novo mutations in schizophrenia implicate synaptic networks , 2014, Nature.

[40]  T. Vos,et al.  Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010 , 2013, The Lancet.

[41]  M. Banasr,et al.  Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. , 2013, The international journal of neuropsychopharmacology.

[42]  M. Bennett,et al.  Stress-Induced Grey Matter Loss Determined by MRI Is Primarily Due to Loss of Dendrites and Their Synapses , 2013, Molecular Neurobiology.

[43]  G. Aghajanian,et al.  Synaptic Dysfunction in Depression: Potential Therapeutic Targets , 2012, Science.

[44]  Yi-xiao Luo,et al.  PI3K/Akt Signaling Pathway in the Basolateral Amygdala Mediates the Rapid Antidepressant-like Effects of Trefoil Factor 3 , 2012, Neuropsychopharmacology.

[45]  Hai-shui Shi,et al.  Green tea polyphenols produce antidepressant-like effects in adult mice. , 2012, Pharmacological research.

[46]  Stephan J Sanders,et al.  Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE. , 2011, Human molecular genetics.

[47]  Y. Bae,et al.  Enhanced NMDA Receptor-Mediated Synaptic Transmission, Enhanced Long-Term Potentiation, and Impaired Learning and Memory in Mice Lacking IRSp53 , 2009, The Journal of Neuroscience.

[48]  R. Weinberg,et al.  Regulation of Dendritic Spine Morphogenesis by Insulin Receptor Substrate 53, a Downstream Effector of Rac1 and Cdc42 Small GTPases , 2005, The Journal of Neuroscience.

[49]  T. Takenawa,et al.  IRSp53/Eps8 Complex Is Important for Positive Regulation of Rac and Cancer Cell Motility/Invasiveness , 2004, Cancer Research.

[50]  J. Bockmann,et al.  ProSAP/Shank postsynaptic density proteins interact with insulin receptor tyrosine kinase substrate IRSp53 , 2002, Journal of neurochemistry.

[51]  M A Mintun,et al.  The hippocampus and depression , 2002, European Psychiatry.

[52]  Anuradha Rao,et al.  Signaling between the actin cytoskeleton and the postsynaptic density of dendritic spines , 2000, Hippocampus.

[53]  M. Abbott,et al.  The Insulin Receptor Tyrosine Kinase Substrate p58/53 and the Insulin Receptor Are Components of CNS Synapses , 1999, The Journal of Neuroscience.