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- Title
GLT-1 loss accelerates cognitive deficit onset in an Alzheimer's disease animal model.
- Authors
Mookherjee P; Green PS; Watson GS; Marques MA; Tanaka K; Meeker KD; Meabon JS; Li N; Zhu P; Olson VG; Cook DG; Mookherjee, Paramita; Green, Pattie S; Watson, G Stennis; Marques, Marcos A; Tanaka, Kohichi; Meeker, Kole D; Meabon, James S; Li, Ning; Zhu, Ping
- Abstract
Glutamate transporters regulate normal synaptic network interactions and prevent neurotoxicity by rapidly clearing extracellular glutamate. GLT-1, the dominant glutamate transporter in the cerebral cortex and hippocampus, is significantly reduced in Alzheimer's disease (AD). However, the role GLT-1 loss plays in the cognitive dysfunction and pathology of AD is unknown. To determine the significance of GLT-1 dysfunction on AD-related pathological processes, mice lacking one allele for GLT-1(+/-) were crossed with transgenic mice expressing mutations of the amyloid-β protein precursor and presenilin-1 (AβPPswe/PS1ΔE9) and investigated at 6 or 9 months of age. Partial loss of GLT-1 unmasked spatial memory deficits in 6-month-old mice expressing AβPPswe/PS1ΔE9, with these mice also exhibiting an increase in the ratio of detergent-insoluble Aβ42/Aβ40. At 9 months both behavioral performance and insoluble Aβ42/Aβ40 ratios among GLT-1(+/+)/AβPPswe/PS1ΔE9 and GLT-1(+/-)/AβPPswe/PS1ΔE9 mice were comparable. These results suggest that deficits in glutamate transporter function compound the effects of familial AD AβPP/PS1 mutant transgenes in younger animals and thus may contribute to early occurring pathogenic processes associated with AD.
- Subjects
PSYCHOLOGICAL aspects of aging; ALZHEIMER'S disease; ANIMAL behavior; ANIMAL experimentation; BIOCHEMISTRY; COGNITION disorders; ENZYME-linked immunosorbent assay; LEARNING; LONGITUDINAL method; PHENOMENOLOGY; MEMBRANE proteins; MICE; GENETIC mutation; PEPTIDES; PROTEIN precursors; RESEARCH funding; WESTERN immunoblotting
- Publication
Journal of Alzheimer's Disease, 2011, Vol 23, Issue 1, p447
- ISSN
1387-2877
- Publication type
journal article
- DOI
10.3233/JAD-2011-110503