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AI helps uncover early cell changes in ALS progression

AI supports breakthrough ALS research
Interneuronal markers investigated in the present study and their circuitry. (A) Schematic of the locomotor circuits in the mammalian lumbar spinal cord. (B) Panel of markers detected throughout the study representing the different interneuron populations of interest. Transcript expression of underlined markers was quantified for characterization of interneuron dysregulation in ALS progression. Credit: Science Advances (2024). DOI: 10.1126/sciadv.adk3229

New research from the University of St Andrews and the University of Copenhagen has harnessed the power of AI to generate new insights into the progression of ALS.

ALS () is a fatal disorder in which motor neurons—the cells that control movement—progressively die. There is no cure for the disease, and life expectancy after diagnosis is generally between two and five years.

The new study, published in Science Advances, responds to the urgent need for new knowledge about ALS in the search for an effective treatment and cure.

The study, led by researchers from the School of Psychology and Neuroscience at the University of St Andrews, in collaboration with the Department of Neuroscience, University of Copenhagen, shows that specific cell circuits that control movement are affected early in the disease, while others are affected later during disease progression.

"By using techniques that allow to simultaneously study multiple cell types in spinal cord tissue, combined with a novel AI-based analysis method, we identified the specific networks of cells affected early in disease before motor neurons die," explains lead researcher Dr. Ilary Allodi, lecturer in Systems Neuroscience at the School of Psychology and Neuroscience.

"These are subgroups of —a type of cell found in the spinal cord known to activate motor neurons."

Ole Kiehn, professor in integrative neuroscience and co-corresponding author of the study, adds, "In healthy individuals, these cell circuits are required to perform movements as walking and running.

"There are specific cells, called inhibitory or excitatory interneurons, which control different aspects of movement by activating . We found that some of these cells are affected at different stages of ALS, with the inhibitory interneurons being affected early on and the excitatory ones being affected later during disease progression."

Researchers developed an AI-based method to facilitate data quantification. "The work uses cutting-edge methodology to identify the cell types contributing to disease," explains Dr. Roser Montañana-Rosell, first author of the study. "These inhibitory and excitatory cells are highly heterogeneous and intermingled within the spinal cord and often difficult to investigate simultaneously.

"The we developed allows to overcome these limitations, while shedding light on potential new targets for treatment." This method is accessible online, with the hope that it will facilitate the completion of other similar studies.

The research was performed in partnership with 10X-Genomics and ACD Bio (Biotechne), two industrial organizations with a leading role in the field of transcriptomics, the technique which enables the identification of cells within the spinal cord.

"We used techniques that allow us to visualize and quantify multiple genes at the same time with single cell resolution in the of the ALS mouse model," says Dr. Allodi.

"Each cell type can be identified by a specific set of genes, but these genes need to be visualized simultaneously. By using these transcriptomic techniques, we were able to differentiate between inhibitory and excitatory populations and among their subpopulations. This allowed us to investigate their fate during different stages of disease progression."

More information: Roser Montañana-Rosell et al, Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS, Science Advances (2024). DOI: 10.1126/sciadv.adk3229

Journal information: Science Advances
Citation: AI helps uncover early cell changes in ALS progression (2024, June 18) retrieved 14 July 2024 from https://medicalxpress.com/news/2024-06-ai-uncover-early-cell-als.html
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