There is little question about whether astrocytes and TDP-43 are related with neurodegenerative diseases and disorders individually. The research looking at both together, however, is considerably less, and demonstrates conflicting results. Usinga cross of two common transgenic mouse models, GFAP-tTA and hTDP-43ΔNLS, to express pathological TDP-43in astrocytesby forcing TDP-43to stay in the cytoplasm, the hypotheses are that there will be non-cell autonomous neurodegeneration, as well as behavioral changes, but that there will be no difference related to when the pathological TDP-43 is expressed or differences based on sex.However, results indicated that under the expression of pathological TDP-43, GFAP-tTA/TDP-43ΔNLS mice demonstrate increased anxiety-like behaviors, with females more affected when the pathological TDP-43 is expressed through development (Early Expression) and males more affected when the pathological TDP-43 is suppressed until after wean (Late Expression). In both males and females, under both Early Expression and Late Expression conditions, the astrocytic expression of TDP-43ΔNLS leads to non-cell autonomous neurodegeneration. In vitro primary coculture of cortical neurons and astrocytes also indicates reduced survivability forcells under the GFAP-tTA/TDP-43ΔNLS condition.
|Commitee:||Lawal, Hakeem, Scott, Derrick, Miletti, Karl, Rosen, Jeff|
|School:||Delaware State University|
|School Location:||United States -- Delaware|
|Source:||DAI-B 82/4(E), Dissertation Abstracts International|
|Keywords:||Astrocytes, Behavior, Development, Neurodegeneration, Sex, TDP-43|
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