Fluorescence spectra of cell markers in the spinal cord for a murine model of amyotrophic lateral sclerosis with heat shock protein overexpression

Abstract

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder with few existing therapies. Fused-in-sarcoma (FUS) gene mutations underlie many cases of ALS worldwide, whereas 70 kDa heat shock protein (HSP70) was shown to be beneficial for neuronal resistance in ALS. In this study, we observed structural changes in the nervous tissue of the spinal cord when FUS and a member of the HSP70 family, HSPA1A, were expressed together. We regarded fluorescent markers of neurons and neuroglial cells in mice with a transgenic FUS model of ALS, comparing them to transgenic animals with HSPA1A overexpression in cells, Hsp70 (in), and in extracellular substance, Hsp70 (out), and to double transgenic mice with both HSPA1A and FUS genes. We revealed the count of neuronal marker NeuN to be significantly decreased in transgenic FUS animals compared to the intact mice from the control group, whereas it increased in double transgenic FUS + Hsp70 (in) animals. The counts of GFAP, astroglial marker, and Iba1, microglial marker, were increased in transgenic FUS mice with a slight but significant decrease in FUS + Hsp70 (in) mice. Overall survival of transgenic FUS animals was less than that of FUS + Hsp70 (in) mice but even higher than the survival of FUS + Hsp70 (out) mice. We consider that HSPA1A in cells of animals with aberrant FUS has a strong impact on their longevity, neuronal survival, and neuroinflammation avoidance. The data from our study outline intracellular HSPA1A as an important target for the development of disease-modifying therapies for FUS-related ALS.

Publication DOI: https://doi.org/10.1088/1612-202X/ada7d8
Divisions: College of Engineering & Physical Sciences > School of Engineering and Technology > Mechanical, Biomedical & Design
College of Engineering & Physical Sciences > Engineering for Health
College of Engineering & Physical Sciences
Funding Information: Authors are grateful to Dr Vladislav O Soldatov for his consultations and fruitful discussion concerning the study. This project is funded by Russian Science Foundation under Grant No. 23-25-00448 from 12.01.2023 (https://rscf.ru/project/23-25-00448/). Th
Additional Information: Copyright © 2025 The Author(s). Published on behalf of Astro Ltd by IOP Publishing Ltd. Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.
Uncontrolled Keywords: immunofluorescence,heat shock protein,HSP70,neurodegeneration,ALS,FUS,spinal cord
Publication ISSN: 1612-202X
Last Modified: 01 Jul 2025 07:18
Date Deposited: 25 Jun 2025 10:45
Full Text Link:
Related URLs: https://iopscie ... 612-202X/ada7d8 (Publisher URL)
PURE Output Type: Article
Published Date: 2025-07
Published Online Date: 2025-06-24
Accepted Date: 2024-12-24
Authors: Piavchenko, Gennadii A.
Pokidova, Ksenia S.
Kuzmin, Egor A.
Venediktov, Artem A.
Meglinski, Igor (ORCID Profile 0000-0002-7613-8191)
Kuznetsov, Sergey L.

Download

[img]

Version: Published Version

License: Creative Commons Attribution


Export / Share Citation


Statistics

Additional statistics for this record