Further Characterization of Intrastriatal Lipopolysaccharide Model of Parkinson's Disease in C57BL/6 Mice.

Larisa Bobrovskaya,Xin-Fu Zhou,Sanjay Garg,Frances Corrigan,Isaac Deng

doi:10.3390/ijms22147380

Abstract

Parkinson’s disease (PD) is the most common movement disorder, characterized by progressive degeneration of the nigrostriatal pathway, which consists of dopaminergic cell bodies in substantia nigra and their neuronal projections to the striatum. Moreover, PD is associated with an array of non-motor symptoms such as olfactory dysfunction, gastrointestinal dysfunction, impaired regulation of the sleep-wake cycle, anxiety, depression, and cognitive impairment. Inflammation and concomitant oxidative stress are crucial in the pathogenesis of PD. Thus, this study aimed to model PD via intrastriatal injection of the inflammagen lipopolysaccharide (LPS)to investigate if the lesion causes olfactory and motor impairments, inflammation, oxidative stress, and alteration in synaptic proteins in the olfactory bulb, striatum, and colon. Ten µg of LPS was injected unilaterally into the striatum of 27 male C57BL/6 mice, and behavioural assessment was conducted at 4 and 8 weeks post-treatment, followed by tissue collection. Intrastriatal LPS induced motor impairment in C57BL/6 mice at 8 weeks post-treatment evidenced by reduced latency time in the rotarod test. LPS also induced inflammation in the striatum characterized by increased expression of microglial marker Iba-1 and astrocytic marker GFAP, with degeneration of dopaminergic neuronal fibres (reduced tyrosine hydroxylase immunoreactivity), and reduction of synaptic proteins and DJ-1 protein. Additionally, intrastriatal LPS induced inflammation, oxidative stress and alterations in synaptic proteins within the olfactory bulb, although this did not induce a significant impairment in olfactory function. Intrastriatal LPS induced mild inflammatory changes in the distal colon, accompanied by increased protein expression of 3-nitrotyrosine-modified proteins. This model recapitulated the major features of PD such as motor impairment and degeneration of dopaminergic neuronal fibres in the striatum, as well as some pathological changes in the olfactory bulb and colon; thus, this model could be suitable for understanding clinical PD and testing neuroprotective strategies.

Highlights

Parkinson’s disease (PD) is the most common movement disorder, characterized by core motor symptoms such as resting tremors, rigidity, bradykinesia, and postural instability [1,2]
Another major neuropathological hallmark of PD is the presence of Lewy bodies/Lewy neurites in the surviving dopaminergic neurons, consisting of abnormal aggregates of αsynuclein protein [4]. α-Synuclein protein plays a major role in synaptic function, and alterations in this protein lead to synaptic dysfunction [4,5,6,7]
DJ-1, Parkin and PINK1 are associated with hereditary PD and they are important for mitochondrial function and protection against oxidative stress [5]

Summary

Introduction

Parkinson’s disease (PD) is the most common movement disorder, characterized by core motor symptoms such as resting tremors, rigidity, bradykinesia, and postural instability [1,2]. PD is associated with non-motor symptoms such as olfactory dysfunction, gastrointestinal dysfunction, impaired regulation of the sleep-wake cycle, anxiety, depression, and cognitive impairment; the pathological processes responsible for these complications are not well understood [1,3]. Another major neuropathological hallmark of PD is the presence of Lewy bodies/Lewy neurites in the surviving dopaminergic neurons, consisting of abnormal aggregates of αsynuclein protein [4]. We aimed to investigate some of these proteins in this study

Objectives

Methods

Results