Amyotrophic lateral sclerosis immunoglobulins G enhance the mobility of Lysotracker-labelled vesicles in cultured rat astrocytes

Abstract

Amyotrophic lateral sclerosis-IgG-enhanced vesicle mobility in astrocytes engages changes in calcium homeostasis.

Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes

“…Overall, the IgG from the control group evoked calcium transients in 7.7 ± 3.9% of cells, whereas ALS IgG evoked a change in 47.5 ± 12.9% of cells, significantly higher (p = 0.0158, Fig. 1F), indicating that ALS IgG strongly affects astrocytic calcium homeostasis, as considered by Stenovec et al [26].…”

“…Our results show that ALS IgG stimulates the release of Ca 2+ from intracellular calcium stores and through plasma membrane SOCEs, which remain to be identified. Furthermore, in a subset of experiments, for which we used the same ALS IgG as in our mobility study of lysotracker-stained acidic vesicles [26], we found a moderate (correlation coefficient R = 0.35) and significant (p < 0.001) positive correlation between the peak increase in [Ca 2+ ] i and the change in vesicle maximal displacement [26] evoked by ALS IgG (data not shown). In agreement with previous functional and neuro-immunological studies in neurons [11,12,14,37] and in astrocytes [26], IgG from patients with sALS, but not from control individuals without ALS, evoked rather complex and transient increases in [Ca 2+ ] i in ∼48% of treated astrocytes (Fig.…”

“…Recently, we have shown that in cultured astrocytes, ALS IgG enhances the mobility of acidic vesicles in a Ca 2+ -dependent way [26]. In the present study, we further investigated the effect of ALS IgG on astrocytic Ca 2+ excitability to gain insight into the signaling pathways involved in astroglial activation in ALS.…”

“…The participants gave informed consent in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. Some of the biological material was used to isolate IgG at the Institute of Virology, Vaccines and Sera-Torlak, Belgrade, Serbia, as described previously [26]. IgG isolated from 7 patients with ALS was used to characterize the ALS IgG cytosolic [Ca 2+ ] response in cultured astrocytes, and IgG isolated from additional 5 patients was used in experiments with pharmacological agents.…”

Astroglial calcium signalling in Alzheimer's disease

“…This deficient astroglial phenotype may be associated with changes in the traffic of intracellular vesicles. In astrocytes exposed to antibodies isolated from ALS patients, a massive alteration in vesicle dynamics and Ca 2+ homeostasis has been reported [79,80]. In the animal model of ALS expressing human mutant superoxide dismutase 1 (Tg(SOD1*G93A)1Gur mice), the emergence of atrophic astrocytes is the earliest pathological signature [81][82][83]; these atrophic astrocytes down-regulate glutamate uptake and become vulnerable to glutamate by themselves.…”