1. The SHH/Gli pathway is reactivated in reactive glia and drives proliferation in response to neurodegeneration-induced lesions.
- Author
-
Pitter KL, Tamagno I, Feng X, Ghosal K, Amankulor N, Holland EC, and Hambardzumyan D
- Subjects
- Animals, Astrocytes drug effects, Astrocytes pathology, Cell Proliferation drug effects, Central Nervous System Agents, Disease Models, Animal, Hippocampus pathology, Hippocampus physiopathology, Kainic Acid, Kruppel-Like Transcription Factors genetics, Mice, Mice, Transgenic, Microglia drug effects, Microglia pathology, Neurodegenerative Diseases pathology, Neurogenesis drug effects, Neurogenesis physiology, Neurons pathology, Neurons physiology, Seizures pathology, Seizures physiopathology, Severity of Illness Index, Signal Transduction drug effects, Veratrum Alkaloids pharmacology, Zinc Finger Protein GLI1, Astrocytes physiology, Cell Proliferation physiology, Hedgehog Proteins metabolism, Kruppel-Like Transcription Factors metabolism, Microglia physiology, Neurodegenerative Diseases physiopathology
- Abstract
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., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
- Full Text
- View/download PDF