title: Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.
abstract: Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer's disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer's disease.
authors.affiliation: Department of Neurology, Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Hascup
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Lynn
authors.affiliation: Department of Neurology, Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Fitzgerald
authors.affiliation: Department of Neurology, Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield.
authors.forename: Shari
authors.initials: S
authors.lastname: Randall
authors.affiliation: Edison Biotechnology Institute, Department of Biomedical Sciences, Ohio University, Athens.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston.|Center on Aging, Medical University of South Carolina, Charleston.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boger
authors.affiliation: Department of Internal Medicine and.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.affiliation: Department of Neurology, Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield.|Department of Pharmacology, Southern Illinois University School of Medicine, Springfield.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Hascup
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003071:Cognition / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000502:physiology*; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D011986:Receptors, Somatotropin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D065853:Spatial Learning
chemical_list: D011986:Receptors, Somatotropin; D018698:Glutamic Acid
keywords: Alzheimer’s disease; Biosensor; Electrode; Health span; Longevity