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.