Lipopolysaccharide animal models of Parkinson’s disease: Recent progress and relevance to clinical disease

Abstract

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.

Lesion-associated microglia and macrophages react with massive phagocytosis for debris clearance and wound healing after LPS-induced dopaminergic depletion

“…The only report comparing both models uses an indirect approach, studying the LPS-induced neuroin ammation in the SNpc after a striatal injection [29]. This is actually the most adequate approach for a PD-like in ammatory reaction since injecting into the striatum avoids the direct damage caused by LPS in the SNpc but generates an indirect microglial activation while structurally preserving the area of interest [6].…”

“…It is clear that intranigral LPS injection generates reliable neuronal loss, which can be suitable for particular scienti c questions [6], but whether the in ammation of this model is comparable to PD-like in ammation is still unclear.…”

“…Thus, understanding neuroin ammatory response in PD is essential to design alternative therapeutic interventions [4,5]. For this to be elucidated, experimental models of parkinsonian-like neuroin ammation are necessary to understand the action of local glial cells, as well as potential in ltrated immune cells, on neurons [6].…”

“…Particularly in vitro, together with interferon gamma (IFN-γ), it is canonically used to skew cells of macrophage lineage to a proin ammatory phenotype [18,19]. In vivo, the direct injection of LPS in the central nervous system (CNS) in rodents has commonly been used to study neuroin ammation, particularly as an in ammationinduced PD model when injected directly into dopaminergic areas, speci cally the SNpc [6,20]. Inducing this proin ammatory phenotype in the CNS has been particularly useful to understand the harmful effects on neurons.…”

The Anti-Neuroinflammatory Role of Anthocyanins and Their Metabolites for the Prevention and Treatment of Brain Disorders

“…LPS-treated mice has been extensively used as a PD model, since various observations revealed that LPS may induce the progressive loss of dopaminergic neurons and motor impairments analogous to the clinical symptoms of PD in humans, which are often correlated with immune dysregulation and the inherent molecular and cellular mechanisms [ 159 , 160 ]. Oral administration of purple sweet potato colors, seen as stable anthocyanins, seemed to be effective in improving the motor disabilities in LPS-treated mice.…”