Transgenic inhibition of astroglial NF-kappaB in experimental autoimmune encephalomyelitis
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ABSTRACT: In the central nervous system (CNS) the transcription factor NF-kappaB is a key regulator of inflammation and secondary injury processes. Following trauma or disease, the expression of NF-kappaB-dependent genes is activated, leading to both protective and detrimental effects on CNS recovery. Here we show that transgenic inactivation of astroglial NF-kappaB in mice (GFAP-IkappaBalpha-dn mice) resulted in dramatic reduction of disease severity and improvement in functional recovery following EAE. This coincided with a higher presence of leukocytes in the cord and brain of transgenic mice at the chronic phase of the disease, when the functional recovery over WT mice was the most significant. We observed that expression of proinflammatory genes in both spinal cord and cerebellum was delayed and reduced, while the loss of neuronal-specific molecules essential for synaptic transmission was limited compared to WT mice. Furthermore, death of retinal ganglion cells in affected retinas was almost abolished, suggesting the activation of neuroprotective mechanisms. Our data indicate that inhibiting NF-kappaB in astrocytes results in neuroprotective effects following EAE, directly implicating astrocytes in the pathophysiology of this disease. Keywords: time course, EAE, transgenic mice, astrocytes, inflammation, cytokines, chemokines
ORGANISM(S): Mus musculus
PROVIDER: GSE10235 | GEO | 2009/01/01
SECONDARY ACCESSION(S): PRJNA108409
REPOSITORIES: GEO
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