ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Leptin-induced spine formation requires TrpC channels and the CaM kinase cascade in the hippocampus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Leptin antagonism improves Rett syndrome phenotype in symptomatic Mecp2-deficient mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Leptin and Associated Neural Pathways Underlying Obesity-Induced Hypertension.Comprehensive Physiology · 2025Review
- Sleep links hippocampal propensity for epileptiform activity to its viscerosensory inputs.Frontiers in neuroscience · 2025Article
- Obese male zucker rats show basilar dendritic retraction in the medial prefrontal cortex.Heliyon · 2024Article
- The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity.Nutrients · 2023Review
- Neural stem cell self-renewal stimulation by store-operated calcium entries in adult mouse area postrema: influence of leptin.Frontiers in cellular neuroscience · 2023Article
- Review
- Leptin signaling and leptin resistance.Medical review (2021) · 2022Review
- Review
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- Harnessing the Power of Leptin: The Biochemical Link Connecting Obesity, Diabetes, and Cognitive Decline.Frontiers in aging neuroscience · 2022Review
- Influence of atherosclerosis on the molecular expression of the TRPC1/BK signal complex in the aortic smooth muscles of mice.Experimental and therapeutic medicine · 2022Article
- Leptin increases GABAergic synaptogenesis through the Rho guanine exchange factor β-PIX in developing hippocampal neurons.Science signaling · 2021Article
- Role of Oxidative Stress and CaFrontiers in cell and developmental biology · 2021Review
- Article
- Leptin down-regulates KCC2 activity and controls chloride homeostasis in the neonatal rat hippocampus.Molecular brain · 2020Article
- Linking Social Cognition to Learning and Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Review
- A Leptin-Mediated Neural Mechanism Linking Breathing to Metabolism.Cell reports · 2020Article
- Leptin stimulates synaptogenesis in hippocampal neurons via KLF4 and SOCS3 inhibition of STAT3 signaling.Molecular and cellular neurosciences · 2020Article
- Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities.Scientific reports · 2020Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Leptin is a critical neurotrophic factor for the development of neuronal pathways and synaptogenesis in the hypothalamus. Leptin receptors are also found in other brain regions, including the hippocampus, and a postnatal surge in leptin correlates with a time of rapid growth of dendritic spines and synapses in the hippocampus. Leptin is critical for normal hippocampal dendritic spine formation as db/db mice, which lack normal leptin receptor signaling, have a reduced number of dendritic spines in vivo. Leptin also positively influences hippocampal behaviors, such as cognition, anxiety, and depression, which are critically dependent on dendritic spine number. What is not known are the signaling mechanisms by which leptin initiates spine formation. Here we show leptin induces the formation of dendritic protrusions (thin headless, stubby and mushroom shaped spines), through trafficking and activation of TrpC channels in cultured hippocampal neurons. Leptin-activation of the TrpC current is dose dependent and blocked by targeted knockdown of the leptin receptor. The nonselective TrpC channel inhibitors SKF96365 and 2-APB or targeted knockdown of TrpC1 or 3, but not TrpC5, channels also eliminate the leptin-induced current. Leptin stimulates the phosphorylation of CaMKIγ and β-Pix within 5 min and their activation is required for leptin-induced trafficking of TrpC1 subunits to the membrane. Furthermore, we show that CaMKIγ, CaMKK, β-Pix, Rac1, and TrpC1/3 channels are all required for both the leptin-sensitive current and leptin-induced spine formation. These results elucidate a critical pathway underlying leptin's induction of dendritic morphological changes that initiate spine and excitatory synapse formation.
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Registered trials
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.