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Astrocytes differentially respond to inflammatory autoimmune insults and imbalances of neural activity
- Source :
- Acta Neuropathologica Communications
- Publication Year :
- 2013
- Publisher :
- BioMed Central, 2013.
-
Abstract
- Background Neuronal activity intimately communicates with blood flow through the blood–brain barrier (BBB) in the central nervous system (CNS). Astrocyte endfeet cover more than 90% of brain capillaries and interact with synapses and nodes of Ranvier. The roles of astrocytes in neurovascular coupling in the CNS remain poorly understood. Results Here we show that astrocytes that are intrinsically different are activated by inflammatory autoimmune insults and alterations of neuronal activity. In the progression of experimental autoimmune encephalomyelitis (EAE), both fibrous and protoplasmic astrocytes were broadly and reversibly activated in the brain and spinal cord, indicated by marked upregulation of glial fibrillary acidic protein (GFAP) and other astrocytic proteins. In early and remitting EAE, upregulated GFAP and astrocytic endfoot water channel aquaporin 4 (AQP4) enclosed white matter lesions in spinal cord, whereas they markedly increased and formed bundles in exacerbated lesions in late EAE. In cerebellar cortex, upregulation of astrocytic proteins correlated with EAE severity. On the other hand, protoplasmic astrocytes were also markedly activated in the brains of ankyrin-G (AnkG) and Kv3.1 KO mice, where neuronal activities are altered. Massive astrocytes replaced degenerated Purkinje neurons in AnkG KO mice. In Kv3.1 KO mice, GFAP staining significantly increased in cerebellar cortex, where Kv3.1 is normally highly expressed, but displayed in a patchy pattern in parts of the hippocampus. Conclusions Thus, astrocytes can detect changes in both blood and neurons, which supports their central role in neurovascular coupling. These studies contribute to the development of new strategies of neuroprotection and repair for various diseases, through activity-dependent regulation of neurovascular coupling.
- Subjects :
- Encephalomyelitis
Ankyrin-G
Severity of Illness Index
0302 clinical medicine
Myelin Sheath
Mice, Knockout
Neurons
0303 health sciences
Experimental autoimmune encephalomyelitis
Glial fibrillary acidic protein
biology
Brain
medicine.anatomical_structure
Aquaporin 4
Shaw Potassium Channels
Spinal Cord
Cerebellar cortex
Female
Astrocyte
Ankyrins
Encephalomyelitis, Autoimmune, Experimental
Central nervous system
Mice, Transgenic
Astrocytic endfeet
Neuroprotection
Pathology and Forensic Medicine
03 medical and health sciences
Cellular and Molecular Neuroscience
Bacterial Proteins
Glial Fibrillary Acidic Protein
medicine
Animals
Vimentin
030304 developmental biology
business.industry
Research
Water channel
medicine.disease
Voltage-gated potassium (Kv) channel
Mice, Inbred C57BL
Luminescent Proteins
nervous system
Astrocytes
Chronic Disease
biology.protein
Neurology (clinical)
business
Neuroscience
Neurovascular coupling
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20515960
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Acta Neuropathologica Communications
- Accession number :
- edsair.doi.dedup.....7dfd5ece0e161dec1b9d4a5ccc90baa6