title: Further characterisation of the LPS model of Parkinson's disease: a comparison of intra-nigral and intra-striatal lipopolysaccharide administration on motor function, microgliosis and nigrostriatal neurodegeneration in the rat.
abstract: Chronic neuroinflammation has been established as one of the many processes involved in the pathogenesis of Parkinson's disease (PD). Because of this, researchers have attempted to replicate this pathogenic feature in animal models using the potent inflammagen, lipopolysaccharide (LPS), in order to gain better understanding of immune-mediated events in PD. However, although the effect of intra-cerebral LPS on neuroinflammation and neurodegeneration has been relatively well characterised, its impact on motor function has been less well studied. Therefore, the aim of this study was to further characterise the neuropathological and behavioural impact of intra-nigral and intra-striatal administration of LPS. To do, LPS (10 μg) or vehicle (sterile saline) were stereotaxically injected into the adult rat substantia nigra or striatum on one side only. The effect of LPS administration on lateralised motor function was assessed using the Corridor, Stepping and Whisker tests for two weeks post-injection, after which, amphetamine-induced rotational asymmetry was completed. Post-mortem, the impact of LPS on nigrostriatal degeneration and microgliosis was assessed using quantitative tyrosine hydroxylase and OX-42 immunohistochemistry respectively. We found that intra-nigral administration of LPS led to localised microgliosis in the substantia nigra and this was accompanied by nigrostriatal neurodegeneration and stable spontaneous motor deficits. In contrast, intra-striatal administration of LPS led to localised microgliosis in the striatum but this did not lead to any nigrostriatal neurodegeneration and only induced transient motor dysfunction. In conclusion, this study reveals the impact of intra-cerebral LPS administration on PD-related neuropathology and motor function, and it indicates that the intra-nigral model may be a highly relevant model as it is associated with stable motor decline underpinned by nigral microgliosis and nigrostriatal neurodegeneration.
authors.affiliation: The Department of Pharmacology & Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland.
authors.forename: Deirdre B
authors.initials: DB
authors.lastname: Hoban
authors.forename: Emer
authors.initials: E
authors.lastname: Connaughton
authors.forename: Catherine
authors.initials: C
authors.lastname: Connaughton
authors.forename: Grace
authors.initials: G
authors.lastname: Hogan
authors.forename: Chloe
authors.initials: C
authors.lastname: Thornton
authors.forename: Padraig
authors.initials: P
authors.lastname: Mulcahy
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Moloney
authors.forename: Eilis
authors.initials: E
authors.lastname: Dowd
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D039481:CD11b Antigen / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009048:Motor Skills / Q000187:drug effects; D010300:Parkinson Disease / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D008070:Lipopolysaccharides; D014446:Tyrosine 3-Monooxygenase