Research Paper Volume 4, Issue 11 pp 755—767
Beneficial effects of novel antagonists of GHRH in different models of Alzheimer's disease
- 1 Endocrine, Polypeptide, and Cancer Institute, Miami Veterans Affairs Medical Center and South Florida VA Foundation for Research and Education, Miami, FL 33125, USA
- 2 Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
- 3 Division of Hematology/Oncology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
- 4 Division of Endocrinology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
- 5 On leave of absence from the Department of Pathophysiology, University of Szeged Medical School, Szeged, H-6701, Hungary
Received: November 20, 2012 Accepted: November 27, 2012 Published: November 29, 2012
https://doi.org/10.18632/aging.100504How to Cite
Abstract
Alzheimer's disease is the most frequent debilitating disorder of the central nervous system. Neuroendocrine mechanisms appear to play an important role in this insidiously developing disease. In the present study, the effects of a recently developed growth hormone-releasing hormone (GHRH) antagonist (MIA-690) were evaluated in vivo observing the behavior of genetically modified “Alzheimer's” 5XFAD mice in a Morris water maze (MWM). The effects of the antagonist were also evaluated in vitro using HCN2 human cortical cell cultures treated with amyloid-β1-42. In vivo, the indices of cognitive performance (latency, cumulative index etc.) were followed up for 6 months. In vitro, the formation of reactive oxygen species, markers of inflammatory and neurohormonal signaling were measured by fluorescent detection, PCR, and ELISA. Accumulation of amyloid-β1-42 rafts and τ filaments in necropsied brain samples was verified with the help of ELISA. In the MWM experiments, MIA-690 decreased escape latency, and, in the brain samples, it inhibited the concentration of amyloid-β1-42 and τ filaments. In cell cultures, the GHRH analog showed anti-oxidative and neuro-protective properties and inhibited the GHRH-growth hormone-insulin like growth factor axis. Our data strongly suggest the merit of further studies with GHRH analogs in models of Alzheimer's disease and in elementary clinical trials.