Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorders which is characterised neuropathologically by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (made predominately of α-synuclein) in the surviving neurons. Animal models of PD have improved our understanding of the disease and have played a critical role in the development of neuroprotective agents. Neuroinflammation has been strongly implicated in the pathogenesis of PD, and recent studies have used lipopolysaccharide (LPS), a component of gram-negative bacteria and a potent activator of microglia cells, to mimic the inflammatory events in clinical PD. Modulating the inflammatory response could ameliorate PD associated complications and thus, it is essential to understand the extent to which LPS models reflect human PD. This review will outline the routes of administration of LPS such as stereotaxic, systemic and intranasal, their ability to recapitulate neuropathological markers of PD, and mechanisms of LPS induced toxicity. We will also discuss the ability of the models to replicate motor symptoms and non-motor symptoms of PD such as gastrointestinal dysfunction, olfactory dysfunction, anxiety, depression and cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment.

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.

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