Pre-conditioning with Remote Photobiomodulation Modulates the Brain Transcriptome and Protects Against MPTP Insult in Mice

Neuroscience. 2019 Feb 21:400:85-97. doi: 10.1016/j.neuroscience.2018.12.050. Epub 2019 Jan 6.

Abstract

Transcranial photobiomodulation (PBM), which involves the application of low-intensity red to near-infrared light (600-1100 nm) to the head, provides neuroprotection in animal models of various neurodegenerative diseases. However, the absorption of light energy by the human scalp and skull may limit the utility of transcranial PBM in clinical contexts. We have previously shown that targeting light at peripheral tissues (i.e. "remote PBM") also provides protection of the brain in an MPTP mouse model of Parkinson's disease, suggesting remote PBM might be a viable alternative strategy for overcoming penetration issues associated with transcranial PBM. This present study aimed to determine an effective pre-conditioning regimen of remote PBM for inducing neuroprotection and elucidate the molecular mechanisms by which remote PBM enhances the resilience of brain tissue. Balb/c mice were irradiated with 670-nm light (4 J/cm2 per day) targeting dorsum and hindlimbs for 2, 5 or 10 days, followed by injection of the parkinsonian neurotoxin MPTP (50 mg/kg) over two consecutive days. Despite no direct irradiation of the head, 10 days of pre-conditioning with remote PBM significantly attenuated MPTP-induced loss of midbrain tyrosine hydroxylase-positive dopaminergic cells and mitigated the increase in FOS-positive neurons in the caudate-putamen complex. Interrogation of the midbrain transcriptome by RNA microarray and pathway enrichment analysis suggested upregulation of cell signaling and migration (including CXCR4+ stem cell and adipocytokine signaling), oxidative stress response pathways and modulation of the blood-brain barrier following remote PBM. These findings establish remote PBM preconditioning as a viable neuroprotective intervention and provide insights into the mechanisms underlying this phenomenon.

Keywords: MPTP; Parkinson’s disease; microarray; mouse model; neuroprotection; photobiomodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / radiation effects*
  • Caudate Nucleus / metabolism
  • Caudate Nucleus / radiation effects
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / radiation effects
  • Low-Level Light Therapy / methods*
  • Male
  • Mice, Inbred BALB C
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / radiotherapy*
  • Pars Compacta / metabolism
  • Pars Compacta / radiation effects
  • Putamen / metabolism
  • Putamen / radiation effects
  • Transcriptome / radiation effects*