title: Cognitive Improvement by Photic Stimulation in a Mouse Model of Alzheimer's Disease.
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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Furong
authors.initials: F
authors.lastname: Wang
authors.forename: Xianwen
authors.initials: X
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zou
authors.forename: Osamu
authors.initials: O
authors.lastname: Uchiumi
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Tokio
authors.initials: T
authors.lastname: Sugai
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Physiology, Kanazawa Medical University, Ishikawa 920-0293, Japan. kato@kanazawa-med.ac.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kato
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology* / Q000523:psychology / Q000628:therapy*; D000818:Animals; D001307:Auditory Perception / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology; D015870:Gene Expression; D000072233:Homer Scaffolding Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D010789:Phototherapy / Q000379:methods*; D046509:Tissue Culture Techniques; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels