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2014 ; 62
(10
): 1595-607
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The SHH/Gli pathway is reactivated in reactive glia and drives proliferation in
response to neurodegeneration-induced lesions
#MMPMID24895267
Pitter KL
; Tamagno I
; Feng X
; Ghosal K
; Amankulor N
; Holland EC
; Hambardzumyan D
Glia
2014[Oct]; 62
(10
): 1595-607
PMID24895267
show ga
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.