Beneficial effects of novel antagonists of GHRH in different models of Alzheimersts's disease

Miklos Jaszberenyi, Ferenc G. Rick, Luca Szalontay, Norman L. Block, Marta Zarandi, Ren Zhi Cai, Andrew V. Schally

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 t 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 t 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.

Original languageEnglish (US)
Pages (from-to)755-767
Number of pages13
JournalAging
Volume4
Issue number11
DOIs
StatePublished - 2012

Keywords

  • 5XFAD mice
  • Alzheimer's disease
  • GHRH
  • Growth hormone-releasing hormone
  • HCN-2 cell line
  • Morris water maze
  • Transgenic model

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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