Facilitation of brain mitochondrial activity by 5-aminolevulinic acid in a mouse model of Alzheimer's disease

Chiori Omori, Rika Motodate, Yuzuha Shiraki, Kyoko Chiba, Yuriko Sobu, Ayano Kimura, Tadashi Nakaya, Hikaru Kondo, Satoshi Kurumiya, Toru Tanaka, Kazuo Yamamoto, Motowo Nakajima, Toshiharu Suzuki, Saori Hata

Research output: Contribution to journalArticlepeer-review

Abstract

The activities of mitochondrial enzymes, which are essential for neural function, decline with age and in age-related disease. In particular, the activity of cytochrome c oxidase (COX/complex IV) decreases in patients with Alzheimer's disease (AD). COX, a mitochondrial inner membrane protein complex that contains heme, plays an essential role in the electron transport chain that generates ATP. Heme synthesis begins with 5-aminolevulinic acid (5-ALA) in mitochondria. 5-ALA synthetase is the rate-limiting enzyme in heme synthesis, suggesting that supplementation with 5-ALA might help preserve mitochondrial activity in the aged brain. We administered a diet containing 5-ALA to triple-transgenic AD (3xTg-AD) model mice for 6 months, starting at 3 months of age. COX activity and protein expression, as well as mitochondrial membrane potential, were significantly higher in brains of 5-ALA-fed mice than in controls. Synaptotagmin protein levels were also significantly higher in 5-ALA-fed mice, suggesting improved preservation of synapses. Although brain Aβ levels tended to decrease in 5-ALA-fed mice, we observed no other significant changes in other biochemical and pathological hallmarks of AD. Nevertheless, our study suggests that daily oral administration of 5-ALA could preserve mitochondrial enzyme activities in the brains of aged individuals, thereby contributing to the preservation of neural activity.

Original languageEnglish
Pages (from-to)538-546
Number of pages9
JournalNutritional Neuroscience
Volume20
Issue number9
DOIs
Publication statusPublished - 2017 Oct 21
Externally publishedYes

Keywords

  • 5-Aminolevulinic acid
  • Aging
  • Alzheimer's disease
  • Amyloid-β
  • Cytochrome c oxidase
  • Synaptotagmin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Neuroscience(all)
  • Nutrition and Dietetics

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