title: GRK5 deficiency leads to susceptibility to intermittent hypoxia-induced cognitive impairment.
abstract: Obstructive sleep apnea (OSA) leads to cognitive impairment in about 25% patients, though it remains elusive what makes one more susceptible than the other to be cognitively impaired. G protein-coupled receptor kinase-5 (GRK5) deficiency is recently found to render subjects more susceptible to cognitive impairment triggered by over-expression of Swedish mutant ß-amyloid precursor protein. This study is to determine whether GRK5 deficiency also renders subjects more susceptible to the OSA-triggered cognitive impairment. Both wild type (WT) and GRK5 knockout (KO) mice were placed in conditions absence and presence of intermittent hypoxia (IH) with 8%/21% O2 90-s cycle for 8h a day for a month, and then followed by behavioral assessments with battery of tasks. We found that the selected IH condition only induced marginally abnormal behavior (slightly elevated anxiety with most others unchanged) in the WT mice but it caused significantly more behavioral deficits in the KO mice, ranging from elevated anxiety, impaired balancing coordination, and impaired short-term spatial memory. These results suggest that GRK5 deficiency indeed makes the mice more susceptible to wide range of behavioral impairments, including cognitive impairments.
authors.affiliation: Laboratory for Alzheimer's Disease and Aging Research, Kansas City Veterans Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Singh
authors.affiliation: Laboratory for Alzheimer's Disease and Aging Research, Kansas City Veterans Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Laboratory for Alzheimer's Disease and Aging Research, Kansas City Veterans Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory for Alzheimer's Disease and Aging Research, Kansas City Veterans Affairs Medical Center, Kansas City, MO 64128, USA; Department of Cognitive Sciences, Beijing Institute of Basic Medical Sciences, Beijing 100850, PR China.
authors.forename: XueFeng
authors.initials: X
authors.lastname: Ding
authors.affiliation: Laboratory for Alzheimer's Disease and Aging Research, Kansas City Veterans Affairs Medical Center, Kansas City, MO 64128, USA; Departments of Neurology, University of Kansas Medical College, Kansas City, KS 66170, USA; Departments of Physiology, University of Kansas Medical College, Kansas City, KS 66170, USA; The University of Kansas Alzheimer's Disease Center, Kansas City, KS 66160, USA. Electronic address: William.Suo@va.gov.
authors.forename: William Z
authors.initials: WZ
authors.lastname: Suo
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000172:deficiency* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006120:Grooming / Q000502:physiology; D000860:Hypoxia / Q000150:complications*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004856:Postural Balance / Q000235:genetics; D011596:Psychomotor Disorders / Q000209:etiology; D012678:Sensation Disorders / Q000209:etiology; D065852:Spatial Memory / Q000502:physiology
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase; D054774:G-Protein-Coupled Receptor Kinase 5; C517895:Grk5 protein, mouse
keywords: Cognitive impairment; GRK5 deficiency; Intermittent hypoxia; Memory; Sleep apnea; Susceptibility