Low-level laser therapy for beta amyloid toxicity in rat hippocampus

Yujiao Lu, Ruimin Wang, Yan Dong, Donovan Tucker, Ningjun Zhao, Md Ejaz Ahmed, Ling Zhu, Timon Cheng Yi Liu, Robert M. Cohen, Quanguang Zhang

Research output: Contribution to journalArticle

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Abstract

Beta amyloid (Aβ) is well accepted to play a central role in the pathogenesis of Alzheimer's disease (AD). The present work evaluated the therapeutic effects of low-level laser irradiation (LLI) on Aβ-induced neurotoxicity in rat hippocampus. Aβ 1–42 was injected bilaterally to the hippocampus CA1 region of adult male rats, and 2-minute daily LLI treatment was applied transcranially after Aβ injection for 5 consecutive days. LLI treatment suppressed Aβ-induced hippocampal neurodegeneration and long-term spatial and recognition memory impairments. Molecular studies revealed that LLI treatment: (1) restored mitochondrial dynamics, by altering fission and fusion protein levels thereby suppressing Aβ-induced extensive fragmentation; (2) suppressed Aβ-induced collapse of mitochondrial membrane potential; (3) reduced oxidized mitochondrial DNA and excessive mitophagy; (4) facilitated mitochondrial homeostasis via modulation of the Bcl-2-associated X protein/B-cell lymphoma 2 ratio and of mitochondrial antioxidant expression; (5) promoted cytochrome c oxidase activity and adenosine triphosphate synthesis; (6) suppressed Aβ-induced glucose-6-phosphate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activity; (7) enhanced the total antioxidant capacity of hippocampal CA1 neurons, whereas reduced the oxidative damage; and (8) suppressed Aβ-induced reactive gliosis, inflammation, and tau hyperphosphorylation. Although development of AD treatments has focused on reducing cerebral Aβ levels, by the time the clinical diagnosis of AD or mild cognitive impairment is made, the brain is likely to have already been exposed to years of elevated Aβ levels with dire consequences for multiple cellular pathways. By alleviating a broad spectrum of Aβ-induced pathology that includes mitochondrial dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, and tau pathology, LLI could represent a new promising therapeutic strategy for AD.

Original languageEnglish (US)
Pages (from-to)165-182
Number of pages18
JournalNeurobiology of Aging
Volume49
DOIs
StatePublished - Jan 1 2017

Fingerprint

Amyloid
Hippocampus
Lasers
Alzheimer Disease
Mitochondrial Degradation
Antioxidants
Mitochondrial Dynamics
Pathology
Therapeutics
bcl-2-Associated X Protein
Gliosis
Long-Term Memory
Mitochondrial Membrane Potential
B-Cell Lymphoma
Therapeutic Uses
Electron Transport Complex IV
Mitochondrial DNA
NADP
Oxidoreductases
Oxidative Stress

Keywords

  • Alzheimer's disease
  • Cognition
  • Inflammation
  • Low-level laser therapy
  • Mitochondrial dysfunction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Low-level laser therapy for beta amyloid toxicity in rat hippocampus. / Lu, Yujiao; Wang, Ruimin; Dong, Yan; Tucker, Donovan; Zhao, Ningjun; Ahmed, Md Ejaz; Zhu, Ling; Liu, Timon Cheng Yi; Cohen, Robert M.; Zhang, Quanguang.

In: Neurobiology of Aging, Vol. 49, 01.01.2017, p. 165-182.

Research output: Contribution to journalArticle

Lu, Y, Wang, R, Dong, Y, Tucker, D, Zhao, N, Ahmed, ME, Zhu, L, Liu, TCY, Cohen, RM & Zhang, Q 2017, 'Low-level laser therapy for beta amyloid toxicity in rat hippocampus', Neurobiology of Aging, vol. 49, pp. 165-182. https://doi.org/10.1016/j.neurobiolaging.2016.10.003
Lu, Yujiao ; Wang, Ruimin ; Dong, Yan ; Tucker, Donovan ; Zhao, Ningjun ; Ahmed, Md Ejaz ; Zhu, Ling ; Liu, Timon Cheng Yi ; Cohen, Robert M. ; Zhang, Quanguang. / Low-level laser therapy for beta amyloid toxicity in rat hippocampus. In: Neurobiology of Aging. 2017 ; Vol. 49. pp. 165-182.
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