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Photobiomodulation-induced changes in a monkey model of Parkinson’s disease: changes in tyrosine hydroxylase cells and GDNF expression in the striatum

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Abstract

Intracranial application of red to infrared light, known also as photobiomodulation (PBM), has been shown to improve locomotor activity and to neuroprotect midbrain dopaminergic cells in rodent and monkey models of Parkinson’s disease. In this study, we explored whether PBM has any influence on the number of tyrosine hydroxylase (TH)+cells and the expression of GDNF (glial-derived neurotrophic factor) in the striatum. Striatal sections of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice and monkeys and 6-hydroxydopamine (6OHDA)-lesioned rats that had PBM optical fibres implanted intracranially (or not) were processed for immunohistochemistry (all species) or western blot analysis (monkeys). In our MPTP monkey model, which showed a clear loss in striatal dopaminergic terminations, PBM generated a striking increase in striatal TH+ cell number, 60% higher compared to MPTP monkeys not treated with PBM and 80% higher than controls. This increase was not evident in our MPTP mouse and 6OHDA rat models, both of which showed minimal loss in striatal terminations. In monkeys, the increase in striatal TH+ cell number in MPTP-PBM cases was accompanied by similar increases in GDNF expression, as determined from western blots, from MPTP and control cases. In summary, these results offer insights into the mechanisms by which PBM generates its beneficial effects, potentially with the use of trophic factors, such as GDNF.

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Acknowledgements

We are forever grateful to Michael J Fox Foundation, Credit Agricole Sud Rhones Alpes, Fondation Philanthropique Edmond J Safra, France Parkinson and the French National Research Agency (ANR Carnot Institute), Tenix corp and Salteri family and our industry partners for funding this work. We thank Sharon Spana, Diane Agay, Fannie Darlot, Guillaume Barboux, Clément Perrin, Cyril Zenga and Mylène D’Orchymont for excellent technical assistance and, in particular, many thanks to Donna Lai, Sheng Hua and James Kang for much help with the western blots. All authors contributed to the experiments and analysis of the results and NEM and JM to the writing of the manuscript. There are no conflicts of interests to declare.

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Correspondence to John Mitrofanis.

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El Massri, N., Lemgruber, A.P., Rowe, I.J. et al. Photobiomodulation-induced changes in a monkey model of Parkinson’s disease: changes in tyrosine hydroxylase cells and GDNF expression in the striatum. Exp Brain Res 235, 1861–1874 (2017). https://doi.org/10.1007/s00221-017-4937-0

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  • DOI: https://doi.org/10.1007/s00221-017-4937-0

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