title: Inflammatory and Glutamatergic Homeostasis Are Involved in Successful Aging.
abstract: Whole body studies using long-lived growth hormone receptor gene disrupted or knock out (GHR-KO) mice report global GH resistance, increased insulin sensitivity, reduced insulin-like growth factor 1 (IGF-1), and cognitive retention in old-age, however, little is known about the neurobiological status of these mice. The aim of this study was to determine if glutamatergic and inflammatory markers that are altered in aging and/or age-related diseases and disorders, are preserved in mice that experience increased healthspan. We examined messenger ribonucleic acid (mRNA) expression levels in the brain of 4- to 6-, 8- to 10-, and 20- to 22-month GHR-KO and normal aging control mice. In the hippocampus, glutamate transporter 1 (GLT-1) and anti-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-p50 were elevated in 8- to 10-month GHR-KO mice compared with age-matched controls. In the hypothalamus, NFκB-p50, NFκB-p65, IGF-1 receptor (IGF-1R), glutamate/aspartate transporter (GLAST), and 2-amino-3-(5-methyl-3-oxo 2,3-dihydro-1,2 oxazol-4-yl) propanoic acid receptor subunit 1 (GluA1) were elevated in 8- to 10- and/or 20- to 22-month GHR-KO mice when comparing genotypes. Finally, interleukin 1-beta (IL-1β) mRNA was reduced in 4- to 6- and/or 8- to 10-month GHR-KO mice compared with normal littermates in all brain areas examined. These data support the importance of decreased brain inflammation in early adulthood and maintained homeostasis of the glutamatergic and inflammatory systems in extended longevity.
authors.affiliation: Department of Neurology and the Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield. ehascup@siumed.edu.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Hascup
authors.affiliation: Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield.
authors.forename: Feiya
authors.initials: F
authors.lastname: Wang
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 Internal Medicine, Southern Illinois University School of Medicine, Springfield.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000502:physiology*; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D012333:RNA, Messenger; C493393:Slc1a3 protein, mouse; D013002:Somatomedins
keywords: Aging; Brain; Cognition; Glutamate; Inflammation; Insulin-like growth factor.