Journal
GLIA
Volume 62, Issue 10, Pages 1595-1607Publisher
WILEY-BLACKWELL
DOI: 10.1002/glia.22702
Keywords
Sonic Hedgehog; neurodegeneration; Gli; astrogliosis; microgliosis
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Funding
- Cleveland Clinic Foundation [NIH/NCI U01-CA160882, NIH/NCI F31 NS076028, MSTP NS076028]
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In response to neurodegeneration, the adult mammalian brain activates a cellular cascade that results in reactive astrogliosis and microgliosis. The mechanism through which astrocytes become reactive and the physiological consequences of their activation in response to neurodegeneration is complex. While the activation and proliferation of astrocytes has been shown to occur during massive neuronal cell death, the functional relationship between these two events has not been clearly elucidated. Here we show that in response to kainic acid- (KA) induced neurodegeneration, the mitogen sonic hedgehog (SHH) is upregulated in reactive astrocytes. SHH activity peaks at 7 days and is accompanied by increased Gli activity and elevated proliferation in several cell types. To determine the functional role of SHH-Gli signaling following KA lesions, we used a pharmacological approach to show that SHH secreted by astrocytes drives the activation and proliferation of astrocytes and microglia. The consequences of SHH-Gli signaling in KA-induced lesions appear to be independent of the severity of neurodegeneration.
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