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
-
Bridge Between Neuroimmunity and Traumatic Brain Injury
Current Pharmaceutical Design The Multiple Aspects of Stroke and Stem Cell Therapy
Current Molecular Medicine Human Neural Stem and Progenitor Cells: In Vitro and In Vivo Properties, and Potential for Gene Therapy and Cell Replacement in the CNS
Current Gene Therapy Current Approaches to Prevention of Contrast Induced Acute Kidney Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry Pathophysiology of the Vascular Wall and its Relevance for Cerebrovascular Disorders in Aged Rodents
Current Neurovascular Research Stem Cells as a Novel Tool for Drug Screening and Treatment of Degenerative Diseases
Current Pharmaceutical Design Spastin Interacts with CRMP2 to Regulate Neurite Outgrowth by Controlling Microtubule Dynamics through Phosphorylation Modifications
CNS & Neurological Disorders - Drug Targets HSV-1-Derived Recombinant and Amplicon Vectors for Gene Transfer and Gene Therapy
Current Gene Therapy Pro-Drugs for Indirect Cannabinoids as Therapeutic Agents
Current Drug Delivery The Potential Use of Hormone-Based Therapeutics for the Treatment of Alzheimers Disease
Current Alzheimer Research Can Trehalose Prevent Neurodegeneration? Insights from Experimental Studies
Current Drug Targets Molecules to Selectively Target Receptors for Treatment of Pain and Neurogenic Inflammation
Recent Patents on Inflammation & Allergy Drug Discovery Non-Selective Cation Channel Blockers: Potential Use in Nervous System Basic Research and Therapeutics
Mini-Reviews in Medicinal Chemistry Double-Faced Role of Human Mesenchymal Stem Cells and their Role/Challenges in Cancer Therapy
Current Stem Cell Research & Therapy Targeting Neurotrophin Receptors in the Central Nervous System
CNS & Neurological Disorders - Drug Targets GSK3 Inhibitors and Disease
Mini-Reviews in Medicinal Chemistry Targeted Delivery of Growth Factors by HSV-Mediated Gene Transfer for Peripheral Neuropathy
Current Gene Therapy Alpha-2 Adrenoceptor Ligands and Opioid Drugs: Pharmacological Interactions of Therapeutic Interest
Current Neuropharmacology Nitric Oxide (NO) Signaling as a Potential Therapeutic Modality Against Psychostimulants
Current Pharmaceutical Design The proNGF-p75NTR-Sortilin Signalling Complex as New Target for the Therapeutic Treatment of Parkinsons Disease
CNS & Neurological Disorders - Drug Targets