A deep look into the progression of Parkinson’s disease

Health News
Tags :
Health News
Share This :


A deep look into the progression of Parkinson's Disease
An EM image with the corresponding NanoSIMS 13C map. Credit: Spataro et al 2023. DOI: 10.1186/s40478-023-01608-8

Parkinson’s disease is a complex neurodegenerative disorder that leads to the deterioration of specific types of neurons in the brain, resulting in a number of motor and non-motor symptoms. It is currently estimated that more than 10 million people in the world are living with Parkinson’s disease, the second most common neurodegenerative disorder after Alzheimer’s. That number is expected to swell up to 14 million by 2040 in what is being referred to as the Parkinson’s pandemic.

One of the key events in Parkinson’s disease is the accumulation of a protein called alpha-synuclein inside neurons. That accumulation disrupts the normal functioning of the cells, giving rise to the symptoms of Parkinson’s and other disorders, and progresses into aggregates called Lewy bodies.

In a new study, researchers from two labs at EPFL have combined their expertise to explore how alpha-synuclein disrupts metabolic processes within neurons. The study is a truly interdisciplinary collaboration between the Bertarelli Platform for Gene Therapy of Bernard Schneider and the group of Anders Meibom at EPFL, with support from EPFL’s Bioelectron Microscopy Core Facility.

The work is published in Acta Neuropathologica Communications.

The researchers used cutting-edge imaging techniques, including an analytical instrument called NanoSIMS (Nanoscale Secondary Ion Mass Spectrometry). NanoSIMS is an “ion microprobe” that combines high spatial resolution (50–150 nm), high-resolution mass spectrometry, and high analytical sensitivity, which allow it to produce sub-cellular maps of metabolic turnover with extreme sensitivity. Meibom’s lab at EPFL has famously used NanoSIMS for a number of ecological and geological studies.

In this study, the researchers combined NanoSIMS with stable isotope labeling, to visualize isotopic variations within tissues at high resolution, providing insights into the metabolic activity of individual cellular compartments and organelles. They combined this with Electron Microscopy to “see” more information from biological samples.

To model Parkinson’s disease, the team used genetically modified rats that overexpressed human alpha-synuclein in one hemisphere of the brain, leaving the other healthy as a control. By comparing the neurons overexpressing alpha-synuclein to those in the control hemisphere, the scientists uncovered significant changes in the way carbon molecules are incorporated and processed within neurons.

One of the most remarkable findings was the effect of alpha-synuclein on the turnover of carbon within neurons. Neurons overexpressing alpha-synuclein showed a heightened overall turnover of macromolecules, suggesting that the accumulation of alpha-synuclein may lead to increased metabolic demands on these cells.

A deep look into the progression of Parkinson's Disease
The CryoNanoSIMS setup at EPFL. Credit: Anders Meibom (EPFL)

The study also found changes in the distribution of carbon between different cellular compartments, such as the nucleus and cytoplasm, which may be influenced by alpha-synuclein’s interaction with DNA and histones.

The metabolic disruptions caused by alpha-synuclein also seem to affect specific organelles: Mitochondria, for example, showed abnormal carbon incorporation and turnover patterns, which agrees with previous studies showing that alpha-synuclein impairs mitochondrial function. Similarly, the Golgi apparatus—responsible for cellular trafficking and communication—exhibited metabolic defects that were likely caused by alpha-synuclein disrupting inter-organelle communication.

“This study shows the potential of the NanoSIMS technology to reveal metabolic changes in the brain, with unprecedented resolution, at the subcellular level,” says Bernard Schneider. “It hands us a tool to study early pathological changes occurring in vulnerable neurons as a consequence of alpha-synuclein accumulation, a mechanism directly linked to Parkinson’s disease.”

More information:
Sofia Spataro, Stable isotope labeling and ultra-high-resolution NanoSIMS imaging reveal alpha-synuclein-induced changes in neuronal metabolism in vivo., Acta Neuropathologica Communications (2023). DOI: 10.1186/s40478-023-01608-8

Citation:
A deep look into the progression of Parkinson’s disease (2023, September 28)
retrieved 28 September 2023
from https://medicalxpress.com/news/2023-09-deep-parkinson-disease.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.





Source link

Leave a Reply

Your email address will not be published. Required fields are marked *

Popular News Posts

Categories

Our Exclusive Products

Our Store

Our mission is simple, offer quality products that make our customers lives better at a reasonable price, while ensuring a hassle-free shopping experience. This means that before we bring a product to market, we test it to ensure that it meets our high-level quality standards. Our customer service team understand our products and can answer most every product related question quickly and efficiently. We strive everyday to meet and exceed our customers’ expectations of quality and support! Should we ever fail to meet this expectation – contact us and we will make it right!

Our Value: We are proud of our product and accomplishments, but we typically don’t shout it from the rooftop. Instead, we prefer to let our product and customers do the talking. Our core values can be recognized in our product. The qualities we strive for include:

Pragmatism: We design simple, useful solutions for common needs
Quality: From design to final product, we strive for durable solutions that work
Originality: Creativity and innovation are what makes our product unique
Design: Our minimalist and bold design language focuses on functionality and simplicity that is timeless

0 +

Top Rated Products

0 +

Happy Customers