Abstract
We previously reported that activity of the large conductance calcium-activated potassium (big-K, BK) channel is suppressed by intracellular Aβ in cortical pyramidal cells, and that this suppression was reversed by expression of the scaffold protein Homer1a in 3xTg Alzheimer’s disease model mice. Homer1a is known to be expressed by physiological photic stimulation (PS) as well. The possibility thus arises that PS also reverses Aβ-induced suppression of BK channels, and thereby improves cognition in 3xTg mice. This possibility was tested here. Chronic application of 6-hour-long PS (frequency, 2 Hz; duty cycle, about 1/10; luminance, 300 lx) daily for 4 weeks improved contextual and tone-dependent fear memory in 3xTg mice and, to a lesser extent, Morris water maze performance as well. Hippocampal long-term potentiation was also enhanced after PS. BK channel activity in cingulate cortex pyramidal cells and lateral amygdalar principal cells, suppressed in 3xTg mice, were facilitated. In parallel, neuronal excitability, elevated in 3xTg mice, was recovered to the control level. Gene expression of BK channel, as well as that of the scaffold protein Homer1a, was found decreased in 3xTg mice and reversed by PS. It is known that Homer1a is an activity-dependently inducible immediate early gene product. Consistently, our previous findings showed that Homer1a induced by electrical stimulation facilitated BK channels. By using Homer1a knockouts, we showed that the present PS-induced BK channel facilitation is mediated by Homer1a expression. We thus propose that PS might be potentially useful as a non-invasive therapeutic measure against Alzheimer’s disease.
Keywords: Alzheimer’s disease, BK channel, cognitive improvement, excitability, Homer1, photic stimulation.
Current Alzheimer Research
Title:Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer’s Disease
Volume: 12 Issue: 9
Author(s): Yu Zhang, Furong Wang, Xianwen Luo, Li Wang, Peng Sun, Min Wang, Yongsheng Jiang, Jingyu Zou, Osamu Uchiumi, Ryo Yamamoto, Tokio Sugai, Kenji Yamamoto and Nobuo Kato
Affiliation:
Keywords: Alzheimer’s disease, BK channel, cognitive improvement, excitability, Homer1, photic stimulation.
Abstract: We previously reported that activity of the large conductance calcium-activated potassium (big-K, BK) channel is suppressed by intracellular Aβ in cortical pyramidal cells, and that this suppression was reversed by expression of the scaffold protein Homer1a in 3xTg Alzheimer’s disease model mice. Homer1a is known to be expressed by physiological photic stimulation (PS) as well. The possibility thus arises that PS also reverses Aβ-induced suppression of BK channels, and thereby improves cognition in 3xTg mice. This possibility was tested here. Chronic application of 6-hour-long PS (frequency, 2 Hz; duty cycle, about 1/10; luminance, 300 lx) daily for 4 weeks improved contextual and tone-dependent fear memory in 3xTg mice and, to a lesser extent, Morris water maze performance as well. Hippocampal long-term potentiation was also enhanced after PS. BK channel activity in cingulate cortex pyramidal cells and lateral amygdalar principal cells, suppressed in 3xTg mice, were facilitated. In parallel, neuronal excitability, elevated in 3xTg mice, was recovered to the control level. Gene expression of BK channel, as well as that of the scaffold protein Homer1a, was found decreased in 3xTg mice and reversed by PS. It is known that Homer1a is an activity-dependently inducible immediate early gene product. Consistently, our previous findings showed that Homer1a induced by electrical stimulation facilitated BK channels. By using Homer1a knockouts, we showed that the present PS-induced BK channel facilitation is mediated by Homer1a expression. We thus propose that PS might be potentially useful as a non-invasive therapeutic measure against Alzheimer’s disease.
Export Options
About this article
Cite this article as:
Zhang Yu, Wang Furong, Luo Xianwen, Wang Li, Sun Peng, Wang Min, Jiang Yongsheng, Zou Jingyu, Uchiumi Osamu, Yamamoto Ryo, Sugai Tokio, Yamamoto Kenji and Kato Nobuo, Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer’s Disease, Current Alzheimer Research 2015; 12 (9) . https://dx.doi.org/10.2174/1567205012666150710115755
DOI https://dx.doi.org/10.2174/1567205012666150710115755 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
- Announcements
Related Articles
-
Midkine: A Promising Molecule for Drug Development to Treat Diseases of the Central Nervous System
Current Pharmaceutical Design Meet the Editorial Board Member
CNS & Neurological Disorders - Drug Targets Application of NMR Screening in Drug Discovery
Current Topics in Medicinal Chemistry PET Radiopharmaceuticals for Personalized Medicine
Current Drug Targets Epilepsy, Theories and Treatment Inside Corpus Hippocraticum
Current Pharmaceutical Design Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy
Current Neurovascular Research Importance of P-gp PET Imaging in Pharmacology
Current Pharmaceutical Design Approaches to Mitochondrial Gene Therapy
Current Gene Therapy The Current WHO Classification of Tumours of the Central Nervous System: Histopathology and Additional Diagnostic Methods
Current Medical Imaging Novel Kynurenic Acid Analogues in the Treatment of Migraine and Neurodegenerative Disorders: Preclinical Studies and Pharmaceutical Design
Current Pharmaceutical Design Nano-Neurotherapeutics (NNTs): An Emergent and Multifaceted Tool for CNS Disorders
Current Drug Metabolism Long-Term Effects of Hypoxia-Reoxygenation on Thioredoxins in Rat Central Nervous System
Current Pharmaceutical Design Functional Roles of Benzothiazole Motif in Antiepileptic Drug Research
Mini-Reviews in Medicinal Chemistry Video Game Addiction: Past, Present and Future
Current Psychiatry Reviews Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction
Current Drug Abuse Reviews Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier with Positron Emission Tomography
Current Pharmaceutical Design Current Clinical Applications of In Vivo Magnetic Resonance Spectroscopy and Spectroscopic Imaging
Current Medical Imaging Current Updates in Transdermal Therapeutic Systems and Their Role in Neurological Disorders
Current Protein & Peptide Science Editorial [Pharmacology and Therapeutic Activity of Purinergic Drugs for Disorders of the Nervous System]
CNS & Neurological Disorders - Drug Targets Phytochemical Analysis with Antioxidant and Cytotoxicity Studies of the Bioactive Principles from Zanthoxylum capense (Small Knobwood)
Anti-Cancer Agents in Medicinal Chemistry