Ischemic injury precipitates neuronal vulnerability in Parkinson's disease: Insights from PINK1 mouse model study and clinical retrospective data

Paola Imbriani, Vincenza D'Angelo, Paola Platania, Giulia Di Lazzaro, Simona Scalise, Chiara Salimei, Ilham El Atiallah, Vito Luigi Colona, Nicola Biagio Mercuri, Paola Bonsi, Antonio Pisani, Tommaso Schirinzi, Giuseppina Martella

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalParkinsonism and Related Disorders
Volume74
DOIs
Publication statusPublished - May 2020

Keywords

  • Ischemia
  • Mitochondria
  • Oxidative stress
  • Parkinson's disease
  • PINK1
  • Vascular risk factors

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

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