Mitochondrial Transfer Ameliorates Cognitive Deficits, Neuronal Loss, and Gliosis in Alzheimer's Disease Mice

Keren Nitzan, Sandrine Benhamron, Michael Valitsky, Eyal E. Kesner, Michal Lichtenstein, Ayal Ben-Zvi, Ezra Ella, Yehudit Segalstein, Ann Saada, Haya Lorberboum-Galski, Hanna Rosenmann

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Pathogenesis of neurodegenerative diseases involves dysfunction of mitochondria, one of the most important cell organelles in the brain, with its most prominent roles in producing energy and regulating cellular metabolism. Here we investigated the effect of transferring active intact mitochondria as a potential therapy for Alzheimer's disease (AD), in order to correct as many mitochondrial functions as possible, rather than a mono-drug related therapy. For this purpose, AD-mice (amyloid-β intracerebroventricularly injected) were treated intravenously (IV) with fresh human isolated mitochondria. One to two weeks later, a significantly better cognitive performance was noticed in the mitochondria treated AD-mice relative to vehicle treated AD-mice, approaching the performance of non-AD mice. We also detected a significant decrease in neuronal loss and reduced gliosis in the hippocampus of treated mice relative to untreated AD-mice. An amelioration of the mitochondrial dysfunction in brain was noticed by the increase of citrate-synthase and cytochrome c oxidase activities relative to untreated AD-mice, reaching activity levels of non-AD-mice. Increased mitochondrial activity was also detected in the liver of mitochondria treated mice. No treatment-related toxicity was noted. Thus, IV mitochondrial transfer may possibly offer a novel therapeutic approach for AD.

Original languageAmerican English
Pages (from-to)587-604
Number of pages18
JournalJournal of Alzheimer's Disease
Volume72
Issue number2
DOIs
StatePublished - 2019

Keywords

  • Alzheimer’s disease
  • amyloid-ICV model
  • cognition
  • mitochondria
  • mitochondrial-transfer

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