Structural Changes Observed in the Piriform Cortex in a Rat Model of Pre-motor Parkinson's Disease.

Marco Sancandi,Emma Victoria Schul,Georgia Economides,Audrey Mercer,Andrew Constanti

doi:10.3389/fncel.2018.00479

Marco Sancandi, Emma Victoria Schul + Show 3 more

Open Access

https://doi.org/10.3389/fncel.2018.00479

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Abstract

Early diagnosis of Parkinson’s disease (PD) offers perhaps, the most promising route to a successful clinical intervention, and the use of an animal model exhibiting symptoms comparable to those observed in PD patients in the early stage of the disease, may facilitate screening of novel therapies for delaying the onset of more debilitating motor and behavioral abnormalities. In this study, a rat model of pre-motor PD was used to study the etiology of hyposmia, a non-motor symptom linked to the early stage of the disease when the motor symptoms have yet to be experienced. The study focussed on determining the effect of a partial reduction of both dopamine and noradrenaline levels on the olfactory cortex. Neuroinflammation and striking structural changes were observed in the model. These changes were prevented by treatment with a neuroprotective drug, a glucagon-like peptide-1 (GLP1) receptor agonist, exendin-4 (EX-4).

Highlights

Parkinson’s disease (PD) is a highly debilitating neurodegenerative disorder associated with degeneration of the nigrostriatal dopaminergic pathway, with no present cure
The staging procedure described by Braak et al (2003, 2004) and Braak and Del Tredici (2017) reported a neurone-to-neurone spread of α-synuclein-containing bodies (Lewy pathology – LP) from the enteric nervous system and olfactory system to the central nervous system (CNS) that was correlated with the appearance and severity of both motor and non-motor symptoms of PD
Levels of DA and NA, measured by High Performance Liquid Chromatography (HPLC) in the substantia nigra pars compacta (SNc) were significantly reduced by 47.6 ± 2.4 and 49.9 ± 1.6%, respectively, in the pre-motor model compared with those measured in the sham animals (Figures 2C,D)

Summary

Introduction

Parkinson’s disease (PD) is a highly debilitating neurodegenerative disorder associated with degeneration of the nigrostriatal dopaminergic pathway, with no present cure. The staging procedure described by Braak et al (2003, 2004) and Braak and Del Tredici (2017) reported a neurone-to-neurone spread of α-synuclein-containing bodies (Lewy pathology – LP) from the enteric nervous system and olfactory system to the central nervous system (CNS) that was correlated with the appearance and severity of both motor and non-motor symptoms of PD The reliability of this staging system, has been challenged over the years with evidence suggesting that the staging of LP may be governed by a combination of selective vulnerability and a possible lack of compensatory mechanisms in place in regions with low synaptic connectivity (Halliday and McCann, 2009; Hunn et al, 2015; Surmeier et al, 2017; proposed by “threshold” theory: Engelender and Isacson, 2017; Rietdijk et al, 2017; Jellinger, 2018) rather than the entry of pathogens via the olfactory bulb (OB) (Rey et al, 2018 for review). There is an agreement that olfactory structures, including the OB, anterior olfactory nucleus (AON) and piriform cortex (PC), are affected in a prodromal phase in which the appearance of hyposmia, a non-motor symptom, precedes the first signs of motor dysfunctions

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