期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 22, 期 3, 页码 819-828出版社
IOS PRESS
DOI: 10.3233/JAD-2010-100873
关键词
Alzheimer's disease; brain temporal lobe; ghrelin; GHS-R; In2-ghrelin variant; neurotensin; NTSR
资金
- Programa Nacional de becas de FPU [FPU-AP20052473]
- CIBERNED [CB06/05/0035]
- Ayudas Predoctorales de formacion en investigacion en salud del Instituto de Salud Carlos III [FI06/00804]
- Programa Ramon y Cajal del Ministerio de Educacion y Ciencia, Spain [RYC-2007-00186]
- Junta de Andalucia [BIO-0139, CTS-01705, CTS-5051]
- Ministerio de Ciencia e Innovacion/FEDER, Spain [BFU2007-60180/BFI, BFU2008-01136/BFI]
- Ministerio de Sanidad, Spain [SAF 2006-02424]
- Noscira [2008/285]
- Comunidad de Madrid [SAL/0202/2006]
- Fundacion M. Botin
- Fundacion R. Areces
- NIDDK [30677]
- Department of Veterans Affairs
- Veterans Health Administration
- Office of Research and Development Merit Award
Ghrelin and neurotensin (NTS) are neuroendocrine peptides that exert opposite effects on food intake and energy homeostasis, but share comparable actions in improving memory and learning. Ghrelin and NTS mediate their effects via receptors with high evolutionary identity: two ghrelin G-protein coupled receptors (GPCRs; GHS-R1a/1b) and three NTS-receptors, two GPCRs (NTSR1/2) and one non-GPCR (NTSR3). Because ghrelin and NTS systems are tightly linked to energy balance regulation and cognitive processes, they have been proposed to be altered in Alzheimer's disease (AD), a dementia syndrome markedly influenced by the metabolic status. Although it has been demonstrated that ghrelin and NTS can attenuate AD-related cognitive impairment, a comprehensive analysis of these systems in AD has not been conducted. Here, we used quantitative real time-RT-PCR to analyze expression of the ghrelin/NTS axis in one of the cortical regions most affected in AD, the temporal gyrus. Results unveiled a striking reduction of mRNA levels for ghrelin, and its newly discovered In2-ghrelin variant, as well as for the enzyme responsible for ghrelin acylation, ghrelin-O-acyltransferase and GHS-R1a, while expression of GHS-R1b was markedly increased. In addition, expression levels of NTSR1 and NTSR2 were profoundly decreased in AD, whereas mRNA levels of NTS only declined slightly, and those of NTSR3 (which is involved in neuronal apoptosis) did not vary. Taken together, our results provide the first quantitative evidence showing that ghrelin/NTS systems are markedly altered in the brain of AD patients, thereby suggesting that these systems may contribute to the severe cognitive deficit observed in this pathology.
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