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Disruption in connexin-based communication is associated with intracellular Ca²⁺ signal alterations in astrocytes from Niemann-Pick type C mice.
- Source :
-
PloS one [PLoS One] 2013 Aug 15; Vol. 8 (8), pp. e71361. Date of Electronic Publication: 2013 Aug 15 (Print Publication: 2013). - Publication Year :
- 2013
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Abstract
- Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (NPC) disease, an autosomal lethal neurodegenerative disorder that is mainly caused by mutations in the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in murine astrocytes affects the functional state of gap junction channels and hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1⁻/⁻) showed reduced intercellular communication via gap junctions and increased hemichannel activity. Similarly, astrocytes of newborn Npc1⁻/⁻ hippocampal slices presented high hemichannel activity, which was completely abrogated by connexin 43 hemichannel blockers and was resistant to inhibitors of pannexin 1 hemichannels. Npc1⁻/⁻ astrocytes also showed more intracellular Ca²⁺ signal oscillations mediated by functional connexin 43 hemichannels and P2Y₁ receptors. Therefore, Npc1⁻/⁻ astrocytes present features of connexin based channels compatible with those of reactive astrocytes and hemichannels might be a novel therapeutic target to reduce neuroinflammation in NPC disease.
- Subjects :
- Adenosine Diphosphate analogs & derivatives
Adenosine Diphosphate pharmacology
Animals
Animals, Newborn
Antibodies pharmacology
Astrocytes drug effects
Astrocytes pathology
Calcium Signaling
Cell Communication drug effects
Cells, Cultured
Connexin 43 antagonists & inhibitors
Connexin 43 genetics
Connexins genetics
Connexins metabolism
Disease Models, Animal
Gap Junctions drug effects
Gene Deletion
Gene Expression Regulation
Hippocampus drug effects
Hippocampus metabolism
Intracellular Signaling Peptides and Proteins
Mice
Mice, Knockout
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Niemann-Pick C1 Protein
Niemann-Pick Disease, Type C pathology
Proteins metabolism
Receptors, Purinergic P2Y1 genetics
Receptors, Purinergic P2Y1 metabolism
Tissue Culture Techniques
Astrocytes metabolism
Calcium metabolism
Connexin 43 metabolism
Gap Junctions metabolism
Niemann-Pick Disease, Type C metabolism
Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23977027
- Full Text :
- https://doi.org/10.1371/journal.pone.0071361