The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

Abstract

We have used the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model to explore whether (i) the neuroprotective effect of near infrared light (NIr) treatment in the SNc is dose-dependent and (ii) the relationship between tyrosine hydroxylase (TH)+ terminal density and glial cells in the caudate-putamen complex (CPu). Mice received MPTP injections (50 mg/kg) and 2 J/cm2 NIr dose with either 2 d or 7 d survival period. In another series, with a longer 14 d survival period, mice had a stronger MPTP regime (100 mg/kg) and either 2 J/cm2 or 4 J/cm2 NIr dose. Brains were processed for routine immunohistochemistry and cell counts were made using stereology. Our findings were that in the 2 d series, no change in SNc TH+ cell number was evident after any treatment. In the 7 d series however, MPTP insult resulted in ∼45% reduction in TH+ cell number; after NIr (2 J/cm2) treatment, many cells were protected from the toxic insult. In the 14 d series, MPTP induced a similar reduction in TH+ cell number. NIr mitigated the loss of TH+ cells, but only at the higher dose of 4 J/cm2; the lower dose of 2 J/cm2 had no neuroprotective effect in this series. The higher dose of NIr, unlike the lower dose, also mitigated the MPTP- induced increase in CPu astrocytes after 14 d; these changes were independent of TH+ terminal density, of which, did not vary across the different experimental groups. In summary, we showed that neuroprotection by NIr irradiation in MPTP-treated mice was dose-dependent; with increasing MPTP toxicity, higher doses of NIr were required to protect cells and reduce astrogliosis.

KEYWORDS:

• tyrosine hydroxylase
• substantia nigra
• neuroprotection

Acknowledgements

We thank Sharon Spana for excellent technical assistance. DMJ is supported by a National Health and Medical Research Council of Australia (NHMRC) Early Career Fellowship.

Declaration of Interest

There was no conflict of interest for any of the authors: CM, NT, DMJ, JS, ALB and JM are full-time members of staff at their respective institutions, while FL, CP and NEM are undergraduate students. All authors contributed to the analysis of the data and the writing of the manuscript. FL, CM, NT, CP, NEM, DMJ, DR and JM contributed to the experimental work. The authors alone are responsible for the content and writing of the article.

We are forever grateful to Tenix corp and Salteri family for funding this work.