The BDNF-FoxO1 Axis in the medial prefrontal cortex modulates depressive-like behaviors induced by chronic unpredictable stress in postpartum female mice.
- Authors
- Liu, Jing; Meng, Fantao; Dai, Juanjuan; Wu, Min; Wang, Wentao; Liu, Cuilan; Zhao, Di; Wang, Hongcai; Zhang, Jingyan; Li, Chen
- Year
- 2020
- Journal
- Molecular brain
- PMID
- 32532322
- DOI
- 10.1186/s13041-020-00631-3
- PMCID
- PMC7291536
Postpartum depression (PPD) is a serious psychiatric disorder, affecting not only the childbearing women but also the health of their offsprings. The brain-derived neurotrophic factor (Bdnf) gene is an important target gene for the study of depression and antidepressant therapy. FoxO1, belonging to the FoxO subfamily is involved in the development of major depressive disorders. However, the role of BDNF and its functional brain regions involved in PPD remains unknown. Here, we report that chronic unpredictable stress (CUS) can produce depression-associated behaviors in postpartum female mice. CUS can decrease total Bdnf mRNA and exon specific mRNAs in the medial prefrontal cortex (mPFC), accompanied by reduced protein levels, that were correlated with depression-related behaviors. Moreover, postpartum, not virgin female mice showed increased susceptibility to subthreshold stress-induced depression-related behaviors. Selective deletion of BDNF in the mPFC induced anhedonia as indicated by reduced sucrose preference and increased latency to food in the novelty suppressed food test in postpartum, but not in virgin female mice. Furthermore, we found that FoxO1 is also decreased in CUS-treated postpartum female mice with a significant correlation with depression-related behaviors. BDNF-specific knockout in the mPFC decreased FoxO1 expression in female mice. Our results indicate that the BDNF-FoxO1 axis in mPFC can regulate depression-related behaviors and stress vulnerability in postpartum female mice.
Depression-related behaviors induced by chronic unpredictable stress in virgin and postpartum female mice. a Schematic of the experimental timeline. b Sucrose preference test (SPT). c Novelty-suppressed food test (NSFT). d Forced swimming test (FST). e Locomotor activity. *p < 0.05, ***p < 0.001 compared with none stress group
Regulation of BDNF expression by chronic unpredictable stress. Total Bdnf mRNA levels in the mPFC (a) and the hippocampus (b) of control and CUS groups. c Immunoblots showing BDNF protein levels in the mPFC of control and CUS groups. d Correlation analysis between SPT, NSFT, or FST and total Bdnf mRNA levels in the mPFC. e Correlation analysis between, SPT, NSFT, or FST and BDNF protein levels in mPFC of CUS mice. f Correlation analysis between SPT, NSFT, or FST and total Bdnf mRNA levels in the hippocampus of CUS mice. ***p < 0.001 compared with control group
Susceptibility to subthreshold stress-induced depression-related behavior in postpartum female mice. a Schematic of the experimental timeline. b Sucrose preference test before stress exposure of virgin and postpartum female mice. c Sucrose preference test (SPT) and forced swimming test (FST) after stress exposure of virgin and postpartum female mice. **p < 0.01, ***p < 0.001 compared with controls
Selective deletion of Bdnf in the mPFC induces depression-related behaviors in postpartum female mice. a Schematic illustration of stereotaxic injection of AAV-Cre or AAV-GFP vectors into the mPFC. b Representative image showing GFP expression at the injection sites. Sale bars = 100 μm. c Schematic of the experimental timeline. d Sucrose preference test. e Novelty-suppressed food test. f Locomotor activity. *p < 0.05, ***p < 0.001 compared with AAV-GFP group
Regulation of FoxO1 expression by chronic unpredictable stress. FoxO1 mRNA levels in the mPFC (a) and the hippocampus (b) of control and CUS groups. c Immunoblots showing FoxO1 protein levels in the mPFC of control and CUS groups. d Correlation analysis between SPT, NSFT, or FST and FoxO1 mRNA levels in the mPFC of CUS mice. e Correlation analysis between, SPT, NSFT, or FST and FoxO1 protein levels in the mPFC of CUS mice. ***p < 0.001 compared with control group
FoxO1 expression level is regulated by BDNF in the mPFC. a Correlation analysis between total Bdnf mRNA level and FoxO1 mRNA or protein levels in the mPFC of CUS treated postpartum female mice. b Schematic of the experimental timeline. c Total Bdnf mRNA level after Bdnf deletion in the mPFC. d Immunoblots showing BDNF and FoxO1 protein levels in the mPFC of the AAV-GFP and AAV-Cre groups. e Correlation analysis between total Bdnf mRNA or protein levels and FoxO1 protein levels. **p < 0.01, ***p < 0.001 compared with AAV-GFP group
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Integrated single-cell multiomic profiling of caudate nucleus suggests key mechanisms in alcohol use disorder. | 2025 | 41083468 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Adverse event reporting of mirtazapine: A disproportionality analysis of FDA adverse event reporting system (FAERS) database from 2004-2024. | Guo K et al. | — | 2025 | → |
| Behavioral and physiological benefits of alpha-pinene in adult rats experiencing chronic stress: A focus on depression and oxidative stress. | Hosseini SS et al. | — | 2025 | → |
| Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior. | Han M et al. | — | 2025 | → |
| Chronic unpredictable stress exposure disrupts testicular function by modulating germ cell-junctional dynamics and Nrf2/HO-1/IKKβ/NF-κB pathway. | Yadav S et al. | — | 2025 | → |
| Computational biological analysis reveals that HIF-1 and FoxO signaling pathways influence cognitive impairment in patients with depression. | Zhuo C et al. | — | 2025 | → |
| Emotional dysregulation following prenatal stress is associated with altered prefrontal cortex responsiveness to an acute challenge in adolescence. | Orso R et al. | — | 2025 | → |
| From Synaptic Plasticity to Neurodegeneration: BDNF as a Transformative Target in Medicine. | Toader C et al. | — | 2025 | → |
| Gestational stress disrupts dopamine and oxytocin signaling in the postpartum reward system of rats: implications for mood, motivation and mothering. | Haim A et al. | — | 2025 | → |
| Integrated single-cell multiomic profiling of caudate nucleus suggests key mechanisms in alcohol use disorder. | Green NC et al. | — | 2025 | → |
| Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic-pituitary-adrenal axis. | Wang Y et al. | — | 2024 | → |
| Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain. | Rayan NA et al. | — | 2024 | → |
| The Effect of Forkhead Box O1 Single Nucleotide Polymorphisms on Cortical Thickness and White Matter Integrity in High Suicide Risk Patients. | Shin D et al. | — | 2024 | → |
| The role of stress in perinatal depression and anxiety - A systematic review. | Schalla MA et al. | — | 2024 | → |
| Medial prefrontal cortical PPM1F alters depression-related behaviors by modifying p300 activity via the AMPK signaling pathway. | Liu J et al. | — | 2023 | → |
| Role of Hippocampal miR-132-3p in Modifying the Function of Protein Phosphatase Mg2+/Mn2+-dependent 1 F in Depression. | Ma X et al. | — | 2023 | → |
| Antidepressant effects of Enterococcus faecalis 2001 through the regulation of prefrontal cortical myelination via the enhancement of CREB/BDNF and NF-κB p65/LIF/STAT3 pathways in olfactory bulbectomized mice. | Takahashi K et al. | — | 2022 | → |
| Comparison of the chronic unpredictable mild stress and the maternal separation in mice postpartum depression modeling. | Zhang Y et al. | — | 2022 | → |
| Experience-Regulated Neuronal Signaling in Maternal Behavior. | Fuentes I et al. | — | 2022 | → |
| Identification of potential therapeutic and diagnostic characteristics of Alzheimer disease by targeting the miR-132-3p/FOXO3a-PPM1F axis in APP/PS1 mice. | Fu X et al. | — | 2022 | → |
| Persimmon leaf extract alleviates chronic social defeat stress-induced depressive-like behaviors by preventing dendritic spine loss via inhibition of serotonin reuptake in mice. | Yu H et al. | — | 2022 | → |
| Prenatal Exposure to L-Citrulline Has Positive Effects on Reflexive Motor Behavior in Newborn Mice. | Haramipour P et al. | — | 2022 | → |
| Regional Differences in BDNF Expression and Behavior as a Function of Sex and Enrichment Type: Oxytocin Matters. | Faraji J et al. | — | 2022 | → |
| Research Progress on Natural Compounds Exerting an Antidepressant Effect through Anti-inflammatory. | Yuan C et al. | — | 2022 | → |
| Sex- and age- dependent effect of pre-gestational chronic stress and mirtazapine treatment on neurobehavioral development of Wistar rat offspring. | Viñas-Noguera M et al. | — | 2022 | → |
| The altered sensitivity of acute stress induced anxiety-related behaviors by modulating insular cortex-paraventricular thalamus-bed nucleus of the stria terminalis neural circuit. | Zhao D et al. | — | 2022 | → |
| Co-expression modules construction by WGCNA and identify potential hub genes and regulation pathways of postpartum depression. | Deng Z et al. | — | 2021 | → |
| Cryptotanshinone ameliorates CUS-induced depressive-like behaviors in mice. | Wang K et al. | — | 2021 | → |
| Depression and Antidepressants During Pregnancy: Craniofacial Defects Due to Stem/Progenitor Cell Deregulation Mediated by Serotonin. | Sánchez N et al. | — | 2021 | → |
| Dysregulated gene-associated biomarkers for Alzheimer's disease and aging. | Li M et al. | — | 2021 | → |
| MicroRNA Let-7e in the Mouse Prefrontal Cortex Differentiates Restraint-Stress-Resilient Genotypes from Susceptible Genotype. | Solich J et al. | — | 2021 | → |
| PPM1F in Dentate Gyrus Modulates Anxiety-Related Behaviors by Regulating BDNF Expression via AKT/JNK/p-H3S10 Pathway. | Meng F et al. | — | 2021 | → |
| Regional Differences in Brain Plasticity and Behaviour as a Function of Sex and Enrichment Type: Oxytocin Matters | Faraji J et al. | — | 2021 | — |
| Regulation of depression-related behaviors by GABAergic neurons in the lateral septum through periaqueductal gray neuronal projections. | Wang D et al. | — | 2021 | → |
| The paraventricular thalamus input to central amygdala controls depression-related behaviors. | Zhao D et al. | — | 2021 | → |