Multiple Intranigral Unilateral LPS Infusion Protocol Generates a Persistent Cognitive Impairment without Cumulative Dopaminergic Impairment

Ana   Marcia   Delattre; Bruno      Carabelli; Marco   Aurélio   Mori; Claudia      Pudell; Danielle   R.B.L. da   Silva; Isabela      Menezes; Paula   R.G.   Kempe; Pedro   Vinícius   Staziaki; Patrícia   A.   Dombrowski; Claudio   da   Cunha; Marcelo   M.S.   Lima; Anete   C.   Ferraz

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.

Keywords: Parkinson’s disease, lipopolysaccharide, cognitive impairment, novel-object recognition test.