Mitochondrial alterations in idiopathic REM-sleep disorder could help to predict Parkinson’s disease onset
Authors:
Gerardo Ongari (1), Cristina Ghezzi (1), Micol Avenali (2,5), Michele Terzaghi (3), Antonio Pisani (4,5), Fabio Blandini (6), Silvia Cerri (1)
Organisations:
1: IRCCS Mondino Foundation, Unit of cellular and molecular neurobiology, Pavia, Italy
2: IRCCS Mondino Foundation, Neurorehab ilitation Unit, IRCCS Mondino Foundation, Pavia, Pavia, Italy
3: IRCCS Mondino Foundation, Unit of Sleep Medicine and Epilepsy, Pavia, Italy
4: IRCCS Mondino Foundation, Movement disorders, Pavia, Italy
5: University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy
6: IRCCS Policlinico Maggiore Hospital, Scientific Director, Milano, Italy
Presenting author:
Gerardo Ongari
Exposition date:
Saturday, September 16, 2023
Exposition position:
122/2
Idiopathic REM sleep disorder (iRBD) represents the most important prodromal marker of Parkinson’s disease (PD). Nevertheless, only few studies investigated the mechanisms involved in the development of PD in iRBD subjects. Since the presence of mitochondrial dysfunctions have been linked to sleep disturbances in PD (Smith et al., 2018; Milanese et al., 2019), we explored mitochondrial alterations in fibroblasts of iRBD subjects, in order to characterize a biochemical predictive profile.
The project involved 36 subjects divided in four groups: 10 healthy subjects, 10 subjects with iRBD, 8 iRBD subjects subsequently converted to PD (RBD-PD) and 8 patients who developed RBD after the diagnosis of PD (PD-RBD). Expression levels of mitochondrial proteins were evaluated by western blotting. The rate of mitochondrial respiration was evaluated using an XFe24 Seahorse Analyzer.
The evaluation of the mitochondrial metabolism revealed a reduction in maximal and spare respiration in all groups with RBD, with and without PD. Furthermore, the RBD-PD subjects showed a decrease of ATP production. The impairment of mitochondrial function in RBD-PD and PD-RBD groups was associated with a decrease in the expression levels of mitochondrial complex I, for PD-RBD subjects, and III and V for RBD-PD. These alterations were associated with mitochondrial fragmentation. iRBD subjects showed similar but less severe alterations.
These findings suggest that mitochondrial alterations observed in the fibroblasts of iRBD subjects may predispose to the worsening of the bioenergetic profile observed in RBD-PDs, indicating a potential mechanism underlying the progression of PD in iRBD patients.
