Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging

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 dynamic...

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Bibliographic Details
Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2017-03, Vol.72 (3), p.329-337
Main Authors: Hascup, Kevin N, Lynn, Mary K, Fitzgerald, Patrick J, Randall, Shari, Kopchick, John J, Boger, Heather A, Bartke, Andrzej, Hascup, Erin R
Format: Article
Language:English
Subjects:
Aging
Aging - physiology
Animals
Cognition & reasoning
Cognition - physiology
Female
Glutamic Acid - physiology
Growth hormones
Memory
Mice
Mice, Knockout
Models, Animal
Original
Receptors, Somatotropin - physiology
Rodents
Signal transduction
Signal Transduction - physiology
Spatial Learning
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Summary: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.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/glw088