Abstract
Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO) and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. We have recently reported that BDNF induces a sustained increase in [Ca2+]i through binding with the truncated TrkB receptor, resulting in activation of the PLC pathway and store-operated calcium entry (SOCE) in rodent microglial cells. Sustained activation of SOCE, possibly mediated by TRP channels, occurred after brief BDNF application and contributed to the maintenance of sustained [Ca2+]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, selective serotonin reuptake inhibitors (SSRIs), including paroxetine or sertraline, potentiated the BDNFinduced increase in [Ca2+]i in rodent microglial cells This article provides a review of recent findings on the role of BDNF in the pathophysiology of neuropsychiatric disorders, especially by focusing on its effect on intracellular Ca2+ signaling in microglial cells.
Keywords: BDNF, microglia, calcium, TRP channels, inflammation, depression, schizophrenia, cytokines, neurotrophins, brain, neuropsychiatric, SSRIs, paroxetine, sertraline
Mini-Reviews in Medicinal Chemistry
Title: Possible Role of BDNF-Induced Microglial Intracellular Ca2+ Elevation in the Pathophysiology of Neuropsychiatric Disorders
Volume: 11 Issue: 7
Author(s): Y. Mizoguchi, A. Monji, T. A. Kato, H. Horikawa, Y. Seki, M. Kasai, S. Kanba and S. Yamada
Affiliation:
Keywords: BDNF, microglia, calcium, TRP channels, inflammation, depression, schizophrenia, cytokines, neurotrophins, brain, neuropsychiatric, SSRIs, paroxetine, sertraline
Abstract: Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO) and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. We have recently reported that BDNF induces a sustained increase in [Ca2+]i through binding with the truncated TrkB receptor, resulting in activation of the PLC pathway and store-operated calcium entry (SOCE) in rodent microglial cells. Sustained activation of SOCE, possibly mediated by TRP channels, occurred after brief BDNF application and contributed to the maintenance of sustained [Ca2+]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, selective serotonin reuptake inhibitors (SSRIs), including paroxetine or sertraline, potentiated the BDNFinduced increase in [Ca2+]i in rodent microglial cells This article provides a review of recent findings on the role of BDNF in the pathophysiology of neuropsychiatric disorders, especially by focusing on its effect on intracellular Ca2+ signaling in microglial cells.
Export Options
About this article
Cite this article as:
Mizoguchi Y., Monji A., A. Kato T., Horikawa H., Seki Y., Kasai M., Kanba S. and Yamada S., Possible Role of BDNF-Induced Microglial Intracellular Ca2+ Elevation in the Pathophysiology of Neuropsychiatric Disorders, Mini-Reviews in Medicinal Chemistry 2011; 11 (7) . https://dx.doi.org/10.2174/138955711795906932
DOI https://dx.doi.org/10.2174/138955711795906932 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Remyelination in Multiple Sclerosis: The Therapeutic Potential of Neural and Mesenchymal Stem/Progenitor Cells
Current Signal Transduction Therapy Potential of Selected Antioxidants for Influenza Chemotherapy
Anti-Infective Agents in Medicinal Chemistry Relaxin Receptors - New Drug Targets for Multiple Disease States
Current Drug Targets Overactive Bladder Syndrome, Detrusor Overactivity and the Botulinum Toxin
Reviews on Recent Clinical Trials Opioids in Neuropathic Pain
Current Pharmaceutical Design Ewing’s Sarcoma Cancer Stem Cell Targeted Therapy
Current Stem Cell Research & Therapy Migraine and Central Sensitization: Clinical Features, Main Comorbidities and Therapeutic Perspectives
Current Rheumatology Reviews Bv8-Prokineticins and their Receptors: Modulators of Pain
Current Pharmaceutical Biotechnology Renin-Angiotensin System in Central Nervous System Diseases and its Interaction with COVID-19
Current Medicinal Chemistry Application of Mesenchymal Stem Cells in the Targeted Gene Therapy for Gastric Cancer
Current Stem Cell Research & Therapy The Valsalva Maneuver and Alzheimers Disease: Is there a link?
Current Alzheimer Research The Endocannabinoid System and Multiple Sclerosis
Current Pharmaceutical Design Diversity and Variability of the Effects of Nicotine on Different Cortical Regions of the Brain. Therapeutic and Toxicological Implications
Central Nervous System Agents in Medicinal Chemistry Membrane Transporters as Determinants of the Pharmacology of Platinum Anticancer Drugs
Current Cancer Drug Targets Natural Anti-inflammatory Compounds as Drug Candidates in Alzheimer’s Disease
Current Medicinal Chemistry Plasticity and Therapeutic Potential of Mesenchymal Stem Cells in the Nervous System
Current Pharmaceutical Design AAV9-coGLB1 Improves Lysosomal Storage and Rescues Central Nervous System Inflammation in a Mutant Mouse Model of GM1 Gangliosidosis
Current Gene Therapy Stem Cell-Derived Oligodendroglial Cells for Therapy in Neurological Diseases
Current Stem Cell Research & Therapy Inhibitors of Nitric Oxide Synthase: What's up and What's Next?
Current Enzyme Inhibition Chronic Progressive Multiple Sclerosis – Pathogenesis of Neurodegeneration and Therapeutic Strategies
Current Neuropharmacology