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ALS-Associated SOD1(G93A) Decreases SERCA Pump Levels and Increases Store-Operated Ca2+ Entry in Primary Spinal Cord Astrocytes from a Transgenic Mouse Model
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 20, International Journal of Molecular Sciences, Vol 20, Iss 20, p 5151 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons (MNs), probably by a combination of cell- and non-cell-autonomous processes. The past decades have brought many important insights into the role of astrocytes in nervous system function and disease, including the implication in ALS pathogenesis possibly through the impairment of Ca2+-dependent astrocyte-MN cross-talk. In this respect, it has been recently proposed that altered astrocytic store-operated Ca2+ entry (SOCE) may underlie aberrant gliotransmitter release and astrocyte-mediated neurotoxicity in ALS. These observations prompted us to a thorough investigation of SOCE in primary astrocytes from the spinal cord of the SOD1(G93A) ALS mouse model in comparison with the SOD1(WT)-expressing controls. To this purpose, we employed, for the first time in the field, genetically-encoded Ca2+ indicators, allowing the direct assessment of Ca2+ fluctuations in different cell domains. We found increased SOCE, associated with decreased expression of the sarco-endoplasmic reticulum Ca2+-ATPase and lower ER resting Ca2+ concentration in SOD1(G93A) astrocytes compared to control cells. Such findings add novel insights into the involvement of astrocytes in ALS MN damage.
- Subjects :
- 0301 basic medicine
Nervous system
amyotrophic lateral sclerosis
Ca
Gliotransmitter
lcsh:Chemistry
0302 clinical medicine
Ca2+ signaling
Orai
SERCA
STIM
astrocytes
endoplasmic reticulum
store-operated Ca2+ entry
transgenic mice
amyotrophic lateral sclerosi
store-operated ca2+ entry
Amyotrophic lateral sclerosis
lcsh:QH301-705.5
Spectroscopy
Chemistry
General Medicine
Computer Science Applications
Store‐operated Ca
medicine.anatomical_structure
entry
signaling
Genetically modified mouse
SOD1
2+
Astrocytes
Endoplasmic reticulum
Transgenic mice
Catalysis
Inorganic Chemistry
03 medical and health sciences
astrocyte
medicine
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
Neurotoxicity
medicine.disease
Spinal cord
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....3134fc7ff6a3e500dca19ef431a11607
- Full Text :
- https://doi.org/10.3390/ijms20205151