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The role of Activin A in the regulation of adult neurogenesis.

Adult neurogenesis is defined as the generation of new nerve cells in the adult central nervous system (CNS). Stimulating neurogenesis may potentially offer a therapeutic approach for neurodegenerative diseases such as Parkinson???s disease. However, it is not clear why neurogenesis does not normally replace neurons lost in these diseases. As a first step to address this problem it is necessary to identify mechanisms that regulate adult neurogenesis in the normal and diseased brain and further, determine if manipulating these mechanisms may offer therapeutic potential. In this thesis, we identify activin A, a member of the transforming growth factor ?? (TGF??) superfamily, as a significant regulator of neurogenesis. We demonstrate that mRNA encoding activin A is expressed after a KA injury, and that inhibition of this activin A profoundly impairs neurogenesis in the hippocampus. Further we demonstrate that activin A impairs gliosis and also has potent anti-inflammatory effects in the injured hippocampus. Finally, we provide evidence that the majority of activin A???s neurogenic effect results from its potent anti-inflammatory actions. Our study draws a clear link between neurogenesis and inflammation in the CNS and is the first to provide evidence that this process is regulated through activin signalling. Since inflammation is now believed to be an important component of many neurological diseases we suggest that therapeutic compounds that enhance activin A signalling may offer a therapeutic approach for treating these diseases by suppressing inflammation and stimulating neurogenesis.

Identiferoai:union.ndltd.org:ADTP/278919
Date January 2007
CreatorsAbdipranoto, Andrea, St. Vincent Clinical School, UNSW
PublisherAwarded by:University of New South Wales. St. Vincent Clinical School
Source SetsAustraliasian Digital Theses Program
LanguageEnglish
Detected LanguageEnglish
RightsCopyright Andrea Abdipranoto, http://unsworks.unsw.edu.au/copyright

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