ArticleThe Journal of physiology2002
Leptin inhibits epileptiform-like activity in rat hippocampal neurones via PI 3-kinase-driven activation of BK channels.
Article in The Journal of physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.
- Leptin: role over central nervous system in epilepsy.BMC neuroscience · 2018Pooled it
- Association Between a Body Shape Index and Epilepsy Among US Adults: Potential Indirect Pathway Through Depressive Symptoms.Brain and behavior · 2026Article
- Targeting Adipokines: A Promising Therapeutic Strategy for Epilepsy.Neurochemical research · 2024Review
- Novel Leptin-Based Therapeutic Strategies to Limit Synaptic Dysfunction in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Regulatory Basis of Adipokines Leptin and Adiponectin in Epilepsy: from Signaling Pathways to Glucose Metabolism.Neurochemical research · 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
- Identification of Adipocytokine Pathway-Related Genes in Epilepsy and Its Effect on the Peripheral Immune Landscape.Brain sciences · 2022Article
- Nonobese Male Patients with Alzheimer's Disease Are Vulnerable to Decrease in Plasma Leptin.Journal of Alzheimer's disease : JAD · 2022Article
- Food for Thought: Leptin and Hippocampal Synaptic Function.Frontiers in pharmacology · 2022Review
- Orexin-A and endocannabinoids are involved in obesity-associated alteration of hippocampal neurogenesis, plasticity, and episodic memory in mice.Nature communications · 2021Article
- The Neuronal Actions of Leptin and the Implications for Treating Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Intracellular interplay between cholecystokinin and leptin signalling for satiety control in rats.Scientific reports · 2020Article
- Better brain connectivity is associated with higher total fat mass and lower visceral adipose tissue in military pilots.Scientific reports · 2020Article
- Leptin Regulation of Synaptic Function at Hippocampal TA-CA1 and SC-CA1 Synapses: Implications for Health and Disease.Neurochemical research · 2019Review
- The Effects of Leptin on Glial Cells in Neurological Diseases.Frontiers in neuroscience · 2019Review
- Developmental Switch of Leptin Action on Network Driven Activity in the Neonatal Rat Hippocampus.Frontiers in cellular neuroscience · 2019Article
- Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin.Neurobiology of aging · 2018Article
- Roles of NaPflugers Archiv : European journal of physiology · 2018Review
- Regulation of Hippocampal Synaptic Function by the Metabolic Hormone, Leptin: Implications for Health and Neurodegenerative Disease.Frontiers in cellular neuroscience · 2018Review
- Zinc/CaMK II Associated-Mitophagy Signaling Contributed to Hippocampal Mossy Fiber Sprouting and Cognitive Deficits Following Neonatal Seizures and Its Regulation by Chronic Leptin Treatment.Frontiers in neurology · 2018Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The obese gene product, leptin is an important circulating satiety factor that regulates energy balance via its actions in the hypothalamus. However, leptin receptors are also expressed in brain regions not directly associated with energy homeostasis, such as the hippocampus. Here, leptin inhibits hippocampal neurones via activation of large conductance Ca(2+)-activated K(+) (BK) channels, a process that may be important in regulating neuronal excitability. We now show that leptin receptor labelling is expressed on somata, dendrites and axons, and is also concentrated at synapses in hippocampal cultures. In functional studies, leptin potently and reversibly reduces epileptiform-like activity evoked in lean, but not leptin-resistant Zucker fa/fa rats. Furthermore, leptin also depresses enhanced Ca(2+) levels evoked following Mg(2+) removal in hippocampal cultures. The ability of leptin to modulate this activity requires activation of BK, but not K(ATP), channels as the effects of leptin were mimicked by the BK channel activator NS-1619, and inhibited by the BK channel inhibitors, iberiotoxin and charybdotoxin. The signalling mechanisms underlying this process involve stimulation of phosphoinositide 3-kinase (PI 3-kinase), but not mitogen-activated protein kinase (MAPK), as two structurally unrelated inhibitors of PI 3-kinase, LY294002 and wortmannin, blocked the actions of leptin. These data indicate that leptin, via PI 3-kinase-driven activation of BK channels, elicits a novel mechanism for controlling neuronal excitability. As uncontrolled excitability in the hippocampus is one underlying cause of temporal lobe epilepsy, this novel action of leptin could provide an alternative therapeutic target in the management of epilepsy.
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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.