TY - JOUR
T1 - Ischemic injury precipitates neuronal vulnerability in Parkinson's disease
T2 - Insights from PINK1 mouse model study and clinical retrospective data
AU - Imbriani, Paola
AU - D'Angelo, Vincenza
AU - Platania, Paola
AU - Di Lazzaro, Giulia
AU - Scalise, Simona
AU - Salimei, Chiara
AU - El Atiallah, Ilham
AU - Colona, Vito Luigi
AU - Mercuri, Nicola Biagio
AU - Bonsi, Paola
AU - Pisani, Antonio
AU - Schirinzi, Tommaso
AU - Martella, Giuseppina
N1 - Funding Information:
No conflict of interest and no funding to declare. We thank Mr Massimo Tolu for assistance and Prof. Giuseppe Sancesario from Tor Vergata University for collaboration.
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Ischemia
KW - Mitochondria
KW - Oxidative stress
KW - Parkinson's disease
KW - PINK1
KW - Vascular risk factors
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U2 - 10.1016/j.parkreldis.2020.04.004
DO - 10.1016/j.parkreldis.2020.04.004
M3 - Article
C2 - 32335490
AN - SCOPUS:85083552144
VL - 74
SP - 57
EP - 63
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -