Effect of Photobiomodulation in Rescuing Lipopolysaccharide-Induced Dopaminergic Cell Loss in the Male Sprague-Dawley Rat.

O’brien O’Brien,Austin Austin

doi:10.3390/biom9080381

Abstract

Photobiomodulation (PBM) provides neuroprotection against dopaminergic cell death and associated motor deficits in rodent and primate models of Parkinson’s disease (PD). However, it has not yet been tested in the lipopolysaccharide (LPS) model of PD, which leads to dopaminergic cell death through microglia-evoked neuroinflammation. We investigated whether transcranial PBM could protect against dopaminergic cell death within the substantia nigra in male Sprague–Dawley rats following supranigral LPS injection. PBM fully protected rats from 10 µg LPS which would have otherwise caused 15% cell loss, but there was no significant neuroprotection at a 20 µg dose that led to a 50% lesion. Cell loss at this dose varied according to the precise site of injection and correlated with increased local numbers of highly inflammatory amoeboid microglia. Twenty microgram LPS caused motor deficits in the cylinder, adjusted stepping and rotarod tests that correlated with dopaminergic cell loss. While PBM caused no significant improvement at the group level, motor performance on all three tests no longer correlated with the lesion size caused by 20 µg LPS in PBM-treated rats, suggesting extranigral motor improvements in some animals. These results provide support for PBM as a successful neuroprotective therapy against the inflammatory component of early PD, provided inflammation has not reached a devastating level, as well as potential benefits in other motor circuitries.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterised by motor deficits such as resting tremor, rigidity, and difficulty in initiating and sustaining voluntary movement [1]
Weight loss is a common concomitant of LPS-induced sickness behaviour in rats, 10 μg LPS led to no decreases in weight in the LPS or Photobiomodulation therapy (PBM) groups
PBM rats at day 6 did not reach statistical significance. These results demonstrate that rotarod performance is affected by a 50% tyrosine hydroxylase (TH)+ cell lesion size following 20 μg LPS, and PBM may be capable of alleviating this by post-surgery day 6

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterised by motor deficits such as resting tremor, rigidity, and difficulty in initiating and sustaining voluntary movement [1]. These symptoms worsen as the disease advances primarily due to the progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNc). In several animal models of PD, including the MPTP and 6-OHDA models, rodents and primates treated with PBM demonstrate attenuated dopaminergic cell loss compared to disease-only animals [7,8,9,10].

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