ArticleProceedings of the National Academy of Sciences of the United States of America2018
Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 72 citations in OpenAlex.
- Irisin-BDNF axis mediates muscle-brain communication: a complete molecular cascade and potential bidirectional feedback from peripheral activation to central protection.Biogerontology · 2026Review
- Gαi1/3 Are Essential for BMP2-Induced Osteogenesis by Bridging BMP Receptors to the Gab1 Signaling Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TrkB promotes the neuronal secretion of soluble Siglec-2 (CD22) to mitigate microglial activation and alleviate depression-like behaviors in male mice.Molecular psychiatry · 2026Article
- FSTL4 interaction with Gαi proteins activates the Akt-mTOR pathway to drive malignant phenotypes in non-small cell lung cancer.Cell communication and signaling : CCS · 2026Article
- Gαi1/3 Is a Novel Regulatory Target for RANKL Signal Transduction and Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial RAB5IF is required for pathological and developmental retinal angiogenesis.Nature communications · 2025Article
- Identification of Gαi1 as a key regulator of tumor progression in nasopharyngeal carcinoma.Discover oncology · 2025Article
- HIF-1 Targeting Intervention Renders Protection From Alzheimer's-Like Pathology in a Humanized Mice Model of HIV Infection.Journal of extracellular vesicles · 2025Article
- Gap junction protein beta 5 interacts with Gαi3 to promote Akt activation and cervical cancer cell growth.Cell death & disease · 2025Article
- Gαi3: a crucial biomarker and therapeutic target in bladder cancer.NPJ precision oncology · 2025Article
- Novel peptidomimetic compounds attenuate hypoxic-ischemic brain injury in neonatal rats.Experimental neurology · 2025Article
- Mitochondrial transcription elongation factor TEFM promotes malignant progression of gliomas.Cancer cell international · 2024Article
- Syn3, a newly developed cyclic peptide and BDNF signaling enhancer, ameliorates retinal ganglion cell degeneration in diabetic retinopathy.Protein & cell · 2024Article
- The critical role of Gαi3 in oral squamous cell carcinoma cell growth.Cell death discovery · 2024Article
- Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer.Cell death & disease · 2024Article
- The Porous SilMA Hydrogel Scaffolds Carrying Dual-Sensitive Paclitaxel Nanoparticles Promote Neuronal Differentiation for Spinal Cord Injury Repair.Tissue engineering and regenerative medicine · 2024Article
- Targeting the mitochondrial protein YME1L to inhibit osteosarcoma cell growth in vitro and in vivo.Cell death & disease · 2024Article
- Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice.Science signaling · 2024Article
- Expression and functional significance of phosphoenolpyruvate carboxykinase 1 in uveal melanoma.Cell death discovery · 2024Article
- Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.Cell reports · 2024Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways. In mouse embryonic fibroblasts (MEFs) and CNS neurons, Gαi1/3 knockdown inhibited BDNF-induced tropomyosin-related kinase B (TrkB) endocytosis, adaptor protein activation, and Akt-mTORC1 and Erk-MAPK signaling. Functional studies show that Gαi1 and Gαi3 knockdown decreases the number of dendrites and dendritic spines in hippocampal neurons. In vivo, hippocampal Gαi1/3 knockdown after bilateral microinjection of lentiviral constructs containing Gαi1 and Gαi3 shRNA elicited depressive behaviors. Critically, exogenous expression of Gαi3 in the hippocampus reversed depressive behaviors in CMS mice. Similar results were observed in Gαi1/Gαi3 double-knockout mice, which exhibited severe depressive behaviors. These results demonstrate that heterotrimeric Gαi1 and Gαi3 proteins are essential for TrkB signaling and that disruption of Gαi1 or Gαi3 function could contribute to depressive behaviors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.