Dataset Information

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

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).

SUBMITTER: Sancandi M

PROVIDER: S-EPMC6296349 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Sancandi Marco M Schul Emma Victoria EV Economides Georgia G Constanti Andrew A Mercer Audrey A

Frontiers in cellular neuroscience 20181210

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 e ...[more]

PMID: 30618629

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Project description:Parkinson's disease (PD) is a movement disorder characterized by the early loss of nigrostriatal dopaminergic pathways producing significant network changes impacting motor coordination. Recently three motor stages of PD have been proposed (a silent period when nigrostriatal loss begins, a prodromal motor period with subtle focal manifestations, and clinical PD) with evidence that motor cortex abnormalities occur to produce clinical PD[8]. We directly assess structural changes in the primary motor cortex and corticospinal tract using parallel analyses of longitudinal clinical and cross-sectional pathological cohorts thought to represent different stages of PD. 18F-FP-CIT positron emission tomography and subtle motor features identified patients with idiopathic rapid-eye-movement sleep behaviour disorder (n = 8) that developed prodromal motor signs of PD. Longitudinal diffusion tensor imaging before and after the development of prodromal motor PD showed higher fractional anisotropy in motor cortex and corticospinal tract compared to controls, indicating adaptive structural changes in motor networks in concert with nigrostriatal dopamine loss. Histological analyses of the white matter underlying the motor cortex showed progressive disorientation of axons with segmental replacement of neurofilaments with α-synuclein, enlargement of myelinating oligodendrocytes and increased density of their precursors. There was no loss of neurons in the motor cortex in early or late pathologically confirmed motor PD compared to controls, although there were early cortical increases in neuronal neurofilament light chain and myelin proteins in association with α-synuclein accumulation. Our results collectively provide evidence of a direct impact of PD on primary motor cortex and its output pathways that begins in the prodromal motor stage of PD with structural changes confirmed in early PD. These adaptive structural changes become considerable as the disease advances potentially contributing to motor PD.

Dataset Information

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

Publications

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

Similar Datasets

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