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- Title
Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.
- Authors
Hascup, Kevin N.; Lynn, Mary K.; Fitzgerald, Patrick J.; Randall, Shari; Kopchick, John J.; Boger, Heather A.; Bartke, Andrzej; Hascup, Erin R.
- 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.
- Subjects
COGNITION; SOMATOTROPIN receptors; SUCCESSFUL aging; ALZHEIMER'S disease; BIOSENSORS; LIFE spans; GLUTAMIC acid; CELL receptors; AGING; ANIMAL experimentation; BIOLOGICAL models; CELLULAR signal transduction; MEMORY; MICE; RESEARCH funding; SPATIAL behavior; CELL physiology
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2017, Vol 72, Issue 3, p329
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/glw088