Abstract
In this study, we investigated the effects of a bioactive high-affinity TrkB receptor agonist 7,8- dihydroxyflavone (7,8 DHF) on neonatal brain injury in female and male mice after hypoxia ischemia (HI). HI was induced by exposure of postnatal day 9 (P9) mice to 10% O2 for 50 minutes at 37°C after unilateral ligation of the left common carotid artery. Animals were randomly assigned to HI-vehicle control group [phosphate buffered saline (PBS), intraperitoneally (i.p.)] or HI + 7,8 DHF-treated groups (5 mg/kg in PBS, i.p at 10 min, 24 h, or with subsequent daily injections up to 7 days after HI). The HI-vehicle control mice exhibited neuronal degeneration in the ipsilateral hippocampus and cortex with increased Fluoro-Jade C positive staining and loss of microtubule associated protein 2 expression. In contrast, the 7,8 DHF-treated mice showed less hippocampal neurodegeneration and astrogliosis, with more profound effects in female than in male mice. Moreover, 7,8 DHF-treated mice improved motor learning and spatial learning at P30-60 compared to the HI-vehicle control mice. Diffusion tensor imaging of ex vivo brain tissues at P90 after HI revealed less reduction of fractional anisotropy values in the ipsilateral corpus callosum of 7,8 DHF-treated brains, which was accompanied with better preserved myelin basic protein expression and CA1 hippocampal structure. Taken together, these findings strongly suggest that TrkB agonist 7,8 DHF is protective against HI-mediated hippocampal neuronal death, white matter injury, and improves neurological function, with a more profound response in female than in male mice.
Keywords: Tyrosine kinase B (TrkB), 7, 8 dihydroxyflavone (7, 8 DHF), brain derived neurotropic factor (BDNF), rotarod test, Morris water maze test, fractional anisotropy.
CNS & Neurological Disorders - Drug Targets
Title:TrkB Receptor Agonist 7, 8 Dihydroxyflavone Triggers Profound Gender- Dependent Neuroprotection in Mice After Perinatal Hypoxia and Ischemia
Volume: 12 Issue: 3
Author(s): Kutluay Uluc, Pınar Kendigelen, Emin Fidan, Louise Zhang, Vishal Chanana, Douglas Kintner, Erinc Akture, Chihwa Song, Keqiang Ye, Dandan Sun, Peter Ferrazzano and Pelin Cengiz
Affiliation:
Keywords: Tyrosine kinase B (TrkB), 7, 8 dihydroxyflavone (7, 8 DHF), brain derived neurotropic factor (BDNF), rotarod test, Morris water maze test, fractional anisotropy.
Abstract: In this study, we investigated the effects of a bioactive high-affinity TrkB receptor agonist 7,8- dihydroxyflavone (7,8 DHF) on neonatal brain injury in female and male mice after hypoxia ischemia (HI). HI was induced by exposure of postnatal day 9 (P9) mice to 10% O2 for 50 minutes at 37°C after unilateral ligation of the left common carotid artery. Animals were randomly assigned to HI-vehicle control group [phosphate buffered saline (PBS), intraperitoneally (i.p.)] or HI + 7,8 DHF-treated groups (5 mg/kg in PBS, i.p at 10 min, 24 h, or with subsequent daily injections up to 7 days after HI). The HI-vehicle control mice exhibited neuronal degeneration in the ipsilateral hippocampus and cortex with increased Fluoro-Jade C positive staining and loss of microtubule associated protein 2 expression. In contrast, the 7,8 DHF-treated mice showed less hippocampal neurodegeneration and astrogliosis, with more profound effects in female than in male mice. Moreover, 7,8 DHF-treated mice improved motor learning and spatial learning at P30-60 compared to the HI-vehicle control mice. Diffusion tensor imaging of ex vivo brain tissues at P90 after HI revealed less reduction of fractional anisotropy values in the ipsilateral corpus callosum of 7,8 DHF-treated brains, which was accompanied with better preserved myelin basic protein expression and CA1 hippocampal structure. Taken together, these findings strongly suggest that TrkB agonist 7,8 DHF is protective against HI-mediated hippocampal neuronal death, white matter injury, and improves neurological function, with a more profound response in female than in male mice.
Export Options
About this article
Cite this article as:
Uluc Kutluay, Kendigelen Pınar, Fidan Emin, Zhang Louise, Chanana Vishal, Kintner Douglas, Akture Erinc, Song Chihwa, Ye Keqiang, Sun Dandan, Ferrazzano Peter and Cengiz Pelin, TrkB Receptor Agonist 7, 8 Dihydroxyflavone Triggers Profound Gender- Dependent Neuroprotection in Mice After Perinatal Hypoxia and Ischemia, CNS & Neurological Disorders - Drug Targets 2013; 12 (3) . https://dx.doi.org/10.2174/18715273113129990061
DOI https://dx.doi.org/10.2174/18715273113129990061 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
-
The Challenges of Blood Pressure Control in Dialysis Patients
Recent Advances in Cardiovascular Drug Discovery (Discontinued) Steroidal Conjugates and Their Pharmacological Applications
Current Medicinal Chemistry Microglial Proteases: Strategic Targets for Neuroprotective Agents
Current Neuropharmacology Survival Signaling Pathways Activated by NMDA Receptors
Current Topics in Medicinal Chemistry Cinnamon Polyphenol Extract Exerts Neuroprotective Activity in Traumatic Brain Injury in Male Mice
CNS & Neurological Disorders - Drug Targets Viral Anti-Inflammatory Reagents: The Potential for Treatment of Arthritic and Vasculitic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia
Current Topics in Medicinal Chemistry Quality, not Quantity: The Role of Natural Products and Chemical Proteomics in Modern Drug Discovery
Combinatorial Chemistry & High Throughput Screening Amyloid-like Fibril Formation by Trypsin in Aqueous Ethanol. Inhibition of Fibrillation by PEG
Protein & Peptide Letters Herpetic (Non-Cytomegalovirus) Retinal Infections in Patients with the Acquired Immunodeficiency Syndrome
Current HIV Research Erythropoietin in Heart Failure and Other Cardiovascular Diseases: Hematopoietic and Pleiotropic Effects
Current Drug Targets - Cardiovascular & Hematological Disorders Molecular Insights into Mechanisms of the Cell Death Program:Role in the Progression of Neurodegenerative Disorders
Current Alzheimer Research Metal Nanoparticles for the Treatment and Diagnosis of Neurodegenerative Brain Diseases
Current Pharmaceutical Design Different Inflammatory Biomarker Patterns in the Cerebro-Spinal Fluid Following Heart Surgery and Major Non-Cardiac Operations
Current Drug Metabolism Molecules to Selectively Target Receptors for Treatment of Pain and Neurogenic Inflammation
Recent Patents on Inflammation & Allergy Drug Discovery Metabolic Effects of Resveratrol in Mammals - a Link Between Improved Insulin Action and Aging
Current Aging Science Structural Requirements to Obtain Highly Potent and Selective 18 kDa Translocator Protein (TSPO) Ligands
Current Topics in Medicinal Chemistry Stem Cell Therapies for Intracerebral Hemorrhages
Current Drug Delivery Is Nitric Oxide Assuming a Janus-Face in The Central Nervous System?
Current Medicinal Chemistry Growth Inhibition of Human Non-Small Lung Cancer Cells H460 By Green Tea and Ginger Polyphenols
Anti-Cancer Agents in Medicinal Chemistry