Neuroprotection against Parkinson’s disease with targeted remote photobiomodulation

Abstract

Current treatments for Parkinson’s disease (PD) are merely symptomatic and do not slow neuronal loss. Transcranial photobiomodulation (PBM) – the irradiation of the head with red to near-infrared light – protects against neurodegeneration in rodent models of PD. However, the attenuation of light energy by the thick human skull might limit the translational potential of this intervention. We have discovered that remote PBM, where light is applied exclusively to the body, also protects the brain. However, the optimal tissue target and wavelength for remote PBM are unknown. This thesis aimed to develop an optimised PD model and experimental pipeline (Chapter 2) and engineer a device for delivering remote PBM (Chapter 3) to assess the neuroprotective efficacy of remote PBM targeted to the abdomen or legs (Chapter 4), and to assess the neuroprotective efficacy of different wavelengths of light for abdomen-directed remote PBM (Chapter 5). Mice were injected with the neurotoxin MPTP (50mg/kg) before 3 weeks of daily 660nm PBM to either the head, abdomen, or legs (n=10 per group). Compared to sham-treated MPTP mice, there was significant rescue of midbrain dopaminergic cells in mice receiving PBM to the head (~60%), abdomen (~80%) and legs (~80%), and a comparable rescue of axonal terminals in the striatum. Only leg-directed remote PBM mitigated MPTP-induced motor deficits. A separate cohort of mice injected with MPTP received abdomen-directed remote PBM of varying wavelength (660, 808, 904 and combined 660+904nm), 3 times per week. Compared to sham-treated MPTP mice, there was significant rescue of midbrain dopaminergic cells in mice receiving 808nm (~130%) and 660+904nm remote PBM (~90%), but not 660nm nor 904nm remote PBM. Both 808nm and 660+904nm remote PBM showed the strongest protective effects on other outcome measures, including the density of axonal terminations in the striatum and of dopaminergic axons in the gut. These findings validate prior observations of remote PBM-induced neuroprotection in mouse models of PD and proffer the abdomen and legs as efficacious treatment sites. The degree of neuroprotection afforded by remote PBM appears to be dependent on wavelength. In summary, remote PBM shows promise as a safe, non-invasive, and effective disease-modifying intervention for people with PD.