ArticleMolecular endocrinology (Baltimore, Md.)2014
Leptin induces hippocampal synaptogenesis via CREB-regulated microRNA-132 suppression of p250GAP.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 79 citations in OpenAlex.
- Impact of physical activity and exercise interventions on white matter integrity in overweight and obese populations: A systematic review and meta-analysis.Comprehensive psychoneuroendocrinology · 2026Review
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- CCK-sensitive C fibers activate NTS leptin receptor-expressing neurons via NMDA receptors.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity.Nutrients · 2023Review
- Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies.International journal of molecular sciences · 2023Review
- Transcriptome analysis reveals genes associated with stem cell activation by physical exercise in the dentate gyrus of aged p16Ink4a knockout mice.Frontiers in cell and developmental biology · 2023Article
- Neurotrophic Factors and Dendritic Spines.Advances in neurobiology · 2023Article
- Identification of microRNAs related with neural germ layer lineage-specific progenitors during reprogramming.Journal of molecular histology · 2022Article
- MicroRNAs and Synaptic Plasticity: From Their Molecular Roles to Response to Therapy.Molecular neurobiology · 2022Review
- Palmitoylated prolactin-releasing peptide treatment had neuroprotective but not anti-obesity effect in fa/fa rats with leptin signaling disturbances.Nutrition & diabetes · 2022Article
- Relationships between plasma expression levels of microRNA-146a and microRNA-132 in epileptic patients and their cognitive, mental and psychological disorders.Bioengineered · 2022Article
- Electroacupuncture Enhances Cognitive Deficits in a Rat Model of Rapid Eye Movement Sleep Deprivation via Targeting MiR-132.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Synaptic disruption and CREB-regulated transcription are restored by KEMBO molecular medicine · 2021Article
- Leptin increases GABAergic synaptogenesis through the Rho guanine exchange factor β-PIX in developing hippocampal neurons.Science signaling · 2021Article
- The important roles of microRNAs in depression: new research progress and future prospects.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Insulin resistance: a connecting link between Alzheimer's disease and metabolic disorder.Metabolic brain disease · 2021Review
- Alternating hemiplegia of childhood: evolution over time and mouse model corroboration.Brain communications · 2021Article
- Adipocytokines: Are they the Theory of Everything?Cytokine · 2020Review
- Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities.Scientific reports · 2020Article
- Leptin Controls Glutamatergic Synaptogenesis and NMDA-Receptor Trafficking via Fyn Kinase Regulation of NR2B.Endocrinology · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Leptin acts in the hippocampus to enhance cognition and reduce depression and anxiety. Cognitive and emotional disorders are associated with abnormal hippocampal dendritic spine formation and synaptogenesis. Although leptin has been shown to induce synaptogenesis in the hypothalamus, its effects on hippocampal synaptogenesis and the mechanism(s) involved are not well understood. Here we show that leptin receptors (LepRs) are critical for hippocampal dendritic spine formation in vivo because db/db mice lacking the long form of the leptin receptor (LepRb) have reduced spine density on CA1 and CA3 neurons. Leptin promotes the formation of mature spines and functional glutamate synapses on hippocampal pyramidal neurons in both dissociated and slice cultures. These effects are blocked by short hairpin RNAs specifically targeting the LepRb and are absent in cultures from db/db mice. Activation of the LepR leads to cAMP response element-binding protein (CREB) phosphorylation and initiation of CREB-dependent transcription via the MAPK kinase/Erk pathway. Furthermore, both Mek/Erk and CREB activation are required for leptin-induced synaptogenesis. Leptin also increases expression of microRNA-132 (miR132), a well-known CREB target, which is also required for leptin-induced synaptogenesis. Last, leptin suppresses the expression of p250GAP, a miR132 target, and this suppression is obligatory for leptin's effects as is the downstream target of p250GAP, Rac1. LepRs appear to be critical in vivo as db/db mice have lowered hippocampal miR132 levels and elevated p250GAP expression. In conclusion, we identify a novel signaling pathway by which leptin increases synaptogenesis through inducing CREB transcription and increasing microRNA-mediated suppression of p250GAP activity, thus removing a known inhibitor of Rac1-stimulated synaptogenesis.
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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.