Details

Autor(en) / Beteiligte

• Ferrucci, Michela
• Lenzi, Paola
• Lazzeri, Gloria
• Busceti, Carla L.
• Frati, Alessandro
• Puglisi-Allegra, Stefano
• Fornai, Francesco

Titel

Combined light and electron microscopy (CLEM) to quantify methamphetamine-induced alpha-synuclein-related pathology

Ist Teil von

• Journal of Neural Transmission, 2024-04, Vol.131 (4), p.335-358

Ort / Verlag

Vienna: Springer Vienna

Erscheinungsjahr

2024

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• Methamphetamine (METH) produces a cytopathology, which is rather specific within catecholamine neurons both in vitro and ex vivo, in animal models and chronic METH abusers. This led some authors to postulate a sort of parallelism between METH cytopathology and cell damage in Parkinson’s disease (PD). In fact, METH increases and aggregates alpha-syn proto-fibrils along with producing spreading of alpha-syn. Although alpha-syn is considered to be the major component of aggregates and inclusions developing within diseased catecholamine neurons including classic Lewy body (LB), at present, no study provided a quantitative assessment of this protein in situ, neither following METH nor in LB occurring in PD. Similarly, no study addressed the quantitative comparison between occurrence of alpha-syn and other key proteins and no investigation measured the protein compared with non-protein structure within catecholamine cytopathology. Therefore, the present study addresses these issues using an oversimplified model consisting of a catecholamine cell line where the novel approach of combined light and electron microscopy (CLEM) was used measuring the amount of alpha-syn, which is lower compared with p62 or poly-ubiquitin within pathological cell domains. The scenario provided by electron microscopy reveals unexpected findings, which are similar to those recently described in the pathology of PD featuring packing of autophagosome-like vesicles and key proteins shuttling autophagy substrates. Remarkably, small seed-like areas, densely packed with p62 molecules attached to poly-ubiquitin within wide vesicular domains occurred. The present data shed new light about quantitative morphometry of catecholamine cell damage in PD and within the addicted brain.