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Theranostics 2022; 12(5):2205-2231. doi:10.7150/thno.70756 This issue Cite

Research Paper

Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model

Luodan Yang1,2, Chongyun Wu2, Emily Parker2, Yong Li2, Yan Dong2, Lorelei Tucker2, Darrell W. Brann2, Hung Wen Lin1, Quanguang Zhang1✉

1. Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, 1501 Kings Highway, LA 71103 USA.
2. Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA.

✉ Corresponding author: Quanguang Zhang, Ph.D., E-mail: qzh001edu.

Citation:
Yang L, Wu C, Parker E, Li Y, Dong Y, Tucker L, Brann DW, Lin HW, Zhang Q. Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model. Theranostics 2022; 12(5):2205-2231. doi:10.7150/thno.70756. https://www.thno.org/v12p2205.htm
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Abstract

Graphic abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly, causing neuronal degeneration and cognitive deficits that significantly impair independence and quality of life for those affected and their families. Though AD is a major neurodegenerative disease with vast avenues of investigation, there is no effective treatment to cure AD or slow disease progression. The present work evaluated the therapeutic effect of long-term photobiomodulation (PBM) treatment with continuous-wave low-level laser on AD and its underlying mechanism.

Methods: PBM was implemented for 2 min, 3 times per week for 16 months in 2-month-old transgenic AD rats. A battery of behavioral tests was performed to measure the effect of PBM treatment on cognitive dysfunction in AD rats. The effects of PBM therapy on typical AD pathologies, including amyloid plaques, intracellular neurofibrillary tangles, neuronal loss, neuronal injury, neuronal apoptosis, and neurodegeneration, were then assessed. The underlying mechanisms were measured using immunofluorescence staining, western blotting analysis, mass spectrometry, primary cortical and hippocampal cell cultures, and related assay kits.

Results: PBM treatment significantly improved the typical AD pathologies of memory loss, amyloid plaques, tau hyperphosphorylation, neuronal degeneration, spine damage, and synaptic loss. PBM treatment had several mechanistic effects which may explain these beneficial effects, including 1) regulation of glial cell polarization and inhibition of neuroinflammation, 2) preservation of mitochondrial dynamics by regulating fission and fusion proteins, and 3) suppression of oxidative damage to DNA, proteins, and lipids. Furthermore, PBM enhanced recruitment of microglia surrounding amyloid plaques by improving the expression of microglial IL-3Rα and astrocytic IL-3, which implies a potential role of PBM in improving Aβ clearance. Finally, our results implicate neuronal hemoglobin in mediating the neuroprotective effect of PBM, as Hbα knockdown abolished the neuroprotective effect of PBM treatment.

Conclusion: Collectively, our data supports the potential use of PBM treatment to prevent or slow the progression of AD and provides new insights into the molecular mechanisms of PBM therapy.

Keywords: Photobiomodulation, TgF344 rats, Microglia recruitment, Mitochondria, Neuronal hemoglobin

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APA
Yang, L., Wu, C., Parker, E., Li, Y., Dong, Y., Tucker, L., Brann, D.W., Lin, H.W., Zhang, Q. (2022). Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model. Theranostics, 12(5), 2205-2231. https://doi.org/10.7150/thno.70756.

ACS
Yang, L.; Wu, C.; Parker, E.; Li, Y.; Dong, Y.; Tucker, L.; Brann, D.W.; Lin, H.W.; Zhang, Q. Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model. Theranostics 2022, 12 (5), 2205-2231. DOI: 10.7150/thno.70756.

NLM
Yang L, Wu C, Parker E, Li Y, Dong Y, Tucker L, Brann DW, Lin HW, Zhang Q. Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model. Theranostics 2022; 12(5):2205-2231. doi:10.7150/thno.70756. https://www.thno.org/v12p2205.htm

CSE
Yang L, Wu C, Parker E, Li Y, Dong Y, Tucker L, Brann DW, Lin HW, Zhang Q. 2022. Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model. Theranostics. 12(5):2205-2231.

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