title: Multiple intranigral unilateral LPS infusion protocol generates a persistent cognitive impairment without cumulative dopaminergic impairment.
abstract: Inflammation in Parkinson's disease (PD) is a continuous process and might be implicated in the progression of neuronal degeneration. Taking this into account, we proposed a new protocol with multiple and consecutive intranigral lipopolysaccharide (LPS) administration in order to analyze its effects on cognitive behavior. Additionally, striatal concentrations of the neurotransmitters dopamine (DA) and serotonin and their respective metabolites were assessed in three different time-points with the purpose of identifying the consecutive and cumulative effects of LPS infusions. We demonstrated that with a minimum administered dose there was stabilization of neuronal damage as revealed by absence of synergic effect on DA concentration. Although the DA decrease (-43%) generates an animal model of early phase of PD, without apparent motor impairment, the LPS group exhibited deficit in episodic-like memory behavior from the first time-point until the last one, indicating persisted disturbances in memory-recognition responses. These findings provide evidence that multiple intranigral LPS infusions are not sufficient to cause cumulative and progressive damage to dopaminergic neurons, but confirm that the LPS model can be adopted as a useful tool providing insight about the cognitive impairment observed in pre-motor phase of PD.
authors.affiliation: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Fisiologia, Av. Francisco H. dos Santos s/n, ZIP: 81.531 - 990, Caixa Postal: 19031, Curitiba, Paraná, Brazil. anete@ufpr.br.
authors.forename: Ana Marcia
authors.initials: AM
authors.lastname: Delattre
authors.forename: Bruno
authors.initials: B
authors.lastname: Carabelli
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Mori
authors.forename: Claudia
authors.initials: C
authors.lastname: Pudell
authors.forename: Danielle R B L
authors.initials: DR
authors.lastname: da Silva
authors.forename: Isabela
authors.initials: I
authors.lastname: Menezes
authors.forename: Paula R G
authors.initials: PR
authors.lastname: Kempe
authors.forename: Pedro Vinícius
authors.initials: PV
authors.lastname: Staziaki
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Dombrowski
authors.forename: Claudio
authors.initials: C
authors.lastname: da Cunha
authors.forename: Marcelo M S
authors.initials: MM
authors.lastname: Lima
authors.forename: Anete C
authors.initials: AC
authors.lastname: Ferraz
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; D012701:Serotonin; D004298:Dopamine