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

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.

Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy

“…Of note, neurotoxic PD models also include pesticides and herbicides, with a particular emphasis on rotenone and paraquat, as environmental factors able to affect PD risk (Vaccari et al, 2019). In addition to these neurotoxins, the administration of high-dose lipopolysaccharide (LPS) has been used to generate animal models of PD (Deng et al, 2021). An alternative to the use of neurotoxins is the generation of genetic models.…”

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

“…For this purpose, we reviewed articles published from 2015 to 2022 using PubMed, Google Scholar and Scopus, related to keywords ‘neuroinflammation’, ‘LPS’, ‘Alzheimer’s disease’, and ‘Parkinson’s disease’. To induce neuroinflammation in the animal model, LPS can be administered intraperitoneally, stereotaxically and intranasally [ 76 ]. A summary of experimental designs carried out in analyzed research papers is demonstrated in the Table 1 .…”

“…Thus, the intrastriatal administration of LPS seems to be superior to the intranigral considering their application in neurodegeneration studies [ 9 ]. Deng and colleagues characterized in the detail the intrastriatal LPS model of PD [ 76 ]. They administered 10 μg of LPS unilaterally and then, after 4 and 8 weeks, behavioral tests were conducted.…”

The Effects of Novel Formulations of Edaravone and Curcumin in the Mouse Intrastriatal Lipopolysaccharide Model of Parkinson’s Disease

“…All the surgical procedures were conducted according to recent studies [21]. Briefly, the mice were deeply anaesthetised via inhalation of isoflurane and mounted onto the stereotaxic frame (motorized stereotaxic apparatus, Stoelting, USA).…”

“…In our recent work, we characterised the intrastriatal LPS model of PD which is beneficial for understanding the neuroinflammatory aspect of the disease [21], and for inves-tigating the efficacy of antioxidants and anti-inflammatory compounds. For this study, we selected to further explore edaravone and curcumin which have been shown to have neuroprotective effects in-vivo due to their antioxidant and anti-inflammatory properties [22][23][24].…”