Experimental Motor Neuron Disease Induced in Mice with Long-Term Repeated Intraperitoneal Injections of Serum from ALS Patients

Izabella Obál,Márta Széll,Valéria Meszlényi,József I Engelhardt,László Siklós,Roland Patai,Gabor G Kovacs,Kornélia Tripolszki,Bernát Nógrádi,Gerda Ricken

doi:10.3390/ijms20102573

Abstract

In an earlier study, signs of commencing degeneration of spinal motor neurons were induced in mice with short-term intraperitoneal injections of immunoglobulin G (IgG) taken from patients with amyotrophic lateral sclerosis (ALS). Since in that study, neither weakness nor loss of motor neurons was noted, to test whether the ALS IgG in this paradigm has the potential to evoke relentless degeneration of motor neurons, treatment with repeated injections over a longer period was carried out. Mice were systematically injected intraperitoneally with serum taken from ALS patients over a 75-day period. At selected time points, the isometric force of the limbs, number of spinal motor neurons and their intracellular calcium levels were determined. Furthermore, markers of glial activation and the motoneuronal uptake of human IgG were monitored. During this period, gliosis and progressive motoneuronal degeneration developed, which led to gradual loss of spinal motor neurons, more than 40% at day 21, along with decreasing muscle strength in the limbs. The inclusion-like accumulation of IgG appeared in the perikarya with the increase of intracellular calcium in the cell bodies and motor nerve terminals. Our results demonstrate that ALS serum can transfer motor neuron disease to mice.

Highlights

Amyotrophic lateral sclerosis (ALS) is a rare but fatal neurodegenerative disease involving upper and lower motor neurons (MNs)
To reduce the number of animals that participated in the study, the number of motor neurons on day 4, 21 and 82 of the experiment was counted in sections set apart from those prepared for thehAistLoSlo-sgeircuomr iminmjecutneodhmistioccehwemeriecanl ocht aarbalcetetroizmataioinnt.aTinhetsheesiercgtiroansspws aesrelostnaginaeldrewadithy hasemeaartolyxyalsind-ay
In our quest to learn more about the pathomechanism of amyotrophic lateral sclerosis (ALS), we decided to transfer the symptoms to mice by using sera taken form ALS patients

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a rare but fatal neurodegenerative disease involving upper (cortical) and lower (brain stem and spinal cord) motor neurons (MNs). Ten percent of the patients had the familiar form of the disease and 90 percent appeared to be sporadic. Genetic alterations were found in both groups. More than 35 major ALS related genes, about 99 ALS risk genes and about 160 alterations of the genes of other neurological diseases were identified in ALS patients. Some genetic alterations may be the targets of future gene therapies [6]. All of these theories lack the explanation of the selective injury of MNs

Methods

Results

Conclusion