Abstract
We have shown previously that near-infrared light (NIr), when applied at the same time as a parkinsonian insult (e.g. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP), reduces behavioural deficits and offers neuroprotection. Here, we explored whether the timing of NIr intervention—either before, at the same time or after the MPTP insult—was important. Mice received MPTP injections (total of 50 mg/kg) and, at various stages in relation to these injections, extracranial application of NIr. Locomotor activity was tested with an open-field test, and brains were processed for immunohistochemistry. Our results showed that regardless of when NIr was applied in relation to MPTP insult, behavioural impairment was reduced by a similar magnitude. The beneficial effect of NIr was fast-acting (within minutes) and long-lasting (for several days). There were more dopaminergic cells in the NIr-treated MPTP groups than in the MPTP group; there was no clear indication that a particular combination of NIr treatment and MPTP injection resulted in a higher cell number. In summary, irrespective of whether it was applied before, at the same time as or after MPTP insult, NIr reduced both behavioural and structural measures of damage by a similar magnitude. There was a broad therapeutic time window of NIr application in relation to the stage of toxic insult, and the NIr was fast-acting and long-lasting.
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Abbreviations
- ATP:
-
Adenosine triphosphate
- LED:
-
Light-emitting diode
- MG:
-
Medial geniculate nucleus
- MPTP:
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- NIr:
-
Near-infrared light
- PaG:
-
Periaqueductal grey matter
- PBS:
-
Phosphate-buffered saline
- Red:
-
Red nucleus
- SNc:
-
Substantia nigra pars compacta
- SNr:
-
Substantia nigra pars reticulata
- TH:
-
Tyrosine hydroxylase
- VTA:
-
Ventral tegmental area
- 6OHDA:
-
6-Hydroxydopamine
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Acknowledgments
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 for funding this work. D.M.J. is an Early Career Fellow of the NHMRC, Australia. J.S. was supported by the Foote Foundation and Sir Zelman Cowen Universities Fund; he is Director of CSCM Pty Ltd.
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C.M., D.M.J., J.S., A.L.B. and J.M. are full-time members of staff at their respective institutions, while F.R. and N.E.M. are postgraduate students. All authors contributed to the analysis of the data and of the reading and writing of the manuscript. F.R., C.M., N.E.M., A.L.B. and J.M. contributed to the experimental work.
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The authors have no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper, except for the funding provided by the organisations mentioned in the Acknowledgements.
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Reinhart, F., El Massri, N., Johnstone, D.M. et al. Near-infrared light (670 nm) reduces MPTP-induced parkinsonism within a broad therapeutic time window. Exp Brain Res 234, 1787–1794 (2016). https://doi.org/10.1007/s00221-016-4578-8
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DOI: https://doi.org/10.1007/s00221-016-4578-8