Ischemic injury precipitates neuronal vulnerability in Parkinson's disease: Insights from PINK1 mouse model study and clinical retrospective data
| Autor: | Paola Platania, Paola Bonsi, Ilham El Atiallah, Tommaso Schirinzi, Paola Imbriani, Giulia Di Lazzaro, Vincenza D'Angelo, Antonio Pisani, Vito Luigi Colona, Giuseppina Martella, Chiara Salimei, Simona Scalise, Nicola Biagio Mercuri |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pathology Parkinson's disease Comorbidity medicine.disease_cause Basal Ganglia Brain Ischemia Mice 0302 clinical medicine Ischemia Risk Factors Basal ganglia Aged 80 and over Mice Knockout Dopaminergic Parkinson Disease Middle Aged Mitochondria Vascular risk factors Neurology Female medicine.medical_specialty PINK1 Settore MED/26 Medium spiny neuron 03 medical and health sciences Oxidative stress Interneurons medicine Animals Humans Vascular Diseases Aged Retrospective Studies business.industry Dopaminergic Neurons medicine.disease Disease Models Animal Oxidative Stress 030104 developmental biology Neurology (clinical) Geriatrics and Gerontology business Protein Kinases 030217 neurology & neurosurgery |
| Zdroj: | Parkinsonism & Related Disorders. 74:57-63 |
| ISSN: | 1353-8020 |
| DOI: | 10.1016/j.parkreldis.2020.04.004 |
| Popis: | Introduction:Increasing evidence demonstrates the relevant association between Parkinson's disease (PD) and vascular diseases/risk factors, as well as a worse clinico-pathological progression in those patients with vascular comorbidity. The mechanisms underlying this relationship have not been clarified yet, although their comprehension is critical in a perspective of disease-modifying treatments development or prevention. Methods:We performed an experimental protocol of ischemic injury (glucose-oxygen deprivation, OGD) on PTEN-induced kinase 1 knockout (PINK1-/-) mice, a well-established PD model, looking at both electrophysiological and morphological changes in basal ganglia. In addition, 253 PD patients were retrospectively analysed, to estimate the prevalence of vascular risk factors. Results:In PINK1-/-mice, the OGD protocol induced electrophysiological (prolonged depolarization) and morphological alterations (picnotic cells, cellular loss and swelling, thickening of nuclear chromatin) in striatal medium spiny neurons and nigral dopaminergic neurons. Vascular comorbidity occurred in 75% of PD patients. Conclusions:The ischemic injury precipitates neuronal vulnerability in basal ganglia of PINK1-/-mice, probably through an impairment of mitochondrial metabolism and higher oxidative stress. These experimental data may provide a potential mechanistic explanation for both the association between vascular diseases and PD and their reciprocal interactions in determining the clinico-pathological burden of PD patients. |
| Databáze: | OpenAIRE |
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