Fibroblast glutamate transport in aging and in AD: correlations with disease severity

Autor: E. Tagliabue, Ildebrando Appollonio, Valeria Isella, Carlo Ferrarese, Marco Racchi, Laura Brighina, Chiara Zoia, Barbara Begni, Lorenzo Fumagalli
Přispěvatelé: Zoia, C, Tagliabue, E, Isella, V, Begni, B, Fumagalli, L, Brighina, L, Appollonio, I, Racchi, M, Ferrarese, C
Rok vydání: 2005
Předmět:
Male
Senescence
Aging
medicine.medical_specialty
Pathology
BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
Amino Acid Transport System X-AG
Statistics as Topic
Glutamic Acid
Biology
Severity of Illness Index
Glutamate Plasma Membrane Transport Proteins
chemistry.chemical_compound
Degenerative disease
Alzheimer Disease
Internal medicine
medicine
Humans
Fibroblast
Neurotransmitter
Cells
Cultured
Aged
MED/26 - NEUROLOGIA
Aged
80 and over
glutamate
EAAT1
aging
Alzheimer's disease
AD
dementia
fibroblasts
Symporters
General Neuroscience
Neurodegeneration
Glutamate receptor
Biological Transport
Fibroblasts
Middle Aged
medicine.disease
Excitatory Amino Acid Transporter 1
medicine.anatomical_structure
Endocrinology
chemistry
Female
Neurology (clinical)
Geriatrics and Gerontology
Alzheimer's disease
Ex vivo
Developmental Biology
Zdroj: Neurobiology of Aging. 26:825-832
ISSN: 0197-4580
DOI: 10.1016/j.neurobiolaging.2004.07.007
Popis: Altered glutamate transport and aberrant EAAT1 expression were shown in Alzheimer’s disease (AD) brains. It is presently unknown whether these modifications are a consequence of neurodegeneration or play a pathogenetic role. However, recent findings of decreased glutamate uptake, EAAT1 protein and mRNA in AD platelets suggest that glutamate transporter modifications may be systemic and might explain the decreased glutamate uptake. We now used primary fibroblast cultures from 10 AD patients to further investigate the specific involvement of glutamate transporters in this disorder and in normal aging. Decreased glutamate uptake (p < 0.001), EAAT1 expression (p < 0.05) and mRNA (p < 0.01) were observed in aged people, compared to younger controls. In AD fibroblasts, compared to age-matched controls, we observed further reductions of glutamate uptake (p < 0.0005) and EAAT1 expression (p < 0.005), while EAAT1 mRNA increase (p < 0.001) was shown. EAAT1 parameters were mutually correlated (p < 0.01) and correlations were shown with dementia severity (p < 0.05 MMSE-expression, p < 0.005 MMSE-mRNA). We suggest fibroblast cultures as possible ex vivo peripheral model to study the glutamate involvement and possible molecular and therapeutic targets in AD.
Databáze: OpenAIRE
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