El Massri Nabil, Lemgruber Ana P, Rowe Isobel J, Moro Cécile, Torres Napoleon, Reinhart Florian, Chabrol Claude, Benabid Alim-Louis, Mitrofanis John
Department of Anatomy F13, University of Sydney, Sydney, 2006, Australia.
University of Grenoble Alpes, CEA, LETI, CLINATEC, MINATEC Campus, 38000, Grenoble, France.
Exp Brain Res. 2017 Jun;235(6):1861-1874. doi: 10.1007/s00221-017-4937-0. Epub 2017 Mar 15.
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.
颅内应用红光至红外光,也称为光生物调节(PBM),已被证明可改善帕金森病啮齿动物和猴子模型的运动活动,并对中脑多巴胺能细胞起到神经保护作用。在本研究中,我们探究了PBM是否对纹状体中酪氨酸羟化酶(TH)细胞的数量以及胶质细胞源性神经营养因子(GDNF)的表达有任何影响。对用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)处理的小鼠和猴子以及用6-羟基多巴胺(6OHDA)损伤且颅内植入(或未植入)PBM光纤的大鼠的纹状体切片进行免疫组织化学处理(所有物种)或蛋白质印迹分析(猴子)。在我们的MPTP猴子模型中,纹状体多巴胺能终末明显减少,PBM使纹状体TH细胞数量显著增加,与未接受PBM处理的MPTP猴子相比高60%,比对照组高80%。在我们的MPTP小鼠和6OHDA大鼠模型中,这种增加并不明显,这两种模型的纹状体终末损失都很小。在猴子中,根据蛋白质印迹法测定,MPTP-PBM组纹状体TH细胞数量的增加伴随着GDNF表达的类似增加,MPTP组和对照组也是如此。总之,这些结果为PBM产生有益作用的机制提供了见解,可能是通过使用营养因子,如GDNF。