Profiling the genes affected by pathogenic TDP-43 in astrocytes Article

Huang, C, Huang, B, Bi, F et al. (2014). Profiling the genes affected by pathogenic TDP-43 in astrocytes . JOURNAL OF NEUROCHEMISTRY, 129(6), 932-939. 10.1111/jnc.12660

cited authors

  • Huang, C; Huang, B; Bi, F; Yan, LH; Tong, J; Huang, J; Xia, XG; Zhou, H

abstract

  • Mutation in TAR DNA binding protein 43 (TDP-43) is a causative factor of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Neurodegeneration may not require the presence of pathogenic TDP-43 in all types of relevant cells. Rather, expression of pathogenic TDP-43 in neurons or astrocytes alone is sufficient to cause cell-Autonomous or non-cell-Autonomous neuron death in transgenic rats. How pathogenic TDP-43 in astrocytes causes non-cell-Autonomous neuron death, however, is not clear. Here, we examined the effect of pathogenic TDP-43 on gene expression in astrocytes. Microarray assay revealed that pathogenic TDP-43 in astrocytes preferentially altered expression of the genes encoding secretory proteins. Whereas neurotrophic genes were down-regulated, neurotoxic genes were up-regulated. Representative genes Lcn2 and chitinase-3-like protein 1 were markedly up-regulated in astrocytes from primary culture and intact transgenic rats. Furthermore, synthetic chitinase-3-like protein 1 induced neuron death in a dose-dependent manner. Our results suggest that TDP-43 pathogenesis is associated with the simultaneous induction of multiple neurotoxic genes in astrocytes, which may synergistically produce adverse effects on neuronal survival and contribute to non-cell-Autonomous neuron death. Restricted expression of pathogenic TDP-43 in astrocytes causes non-cell-Autonomous motor neuron death in transgenic rats. As revealed by microarray assay, pathogenic TDP-43 in astrocytes preferentially altered expression of the genes encoding secretory proteins. Whereas neurotrophic genes were down-regulated, neurotoxic genes were up-regulated. Therefore, TDP-43 pathogenesis is associated with simultaneous induction of neurotoxic genes and repression of neurotrophic genes in astrocytes. Restricted expression of pathogenic TDP-43 in astrocytes causes non-cell-Autonomous motor neuron death in transgenic rats. As revealed by microarray assay, pathogenic TDP-43 in astrocytes preferentially altered expression of the genes encoding secretory proteins. Whereas neurotrophic genes were down-regulated, neurotoxic genes were up-regulated. Therefore, TDP-43 pathogenesis is associated with simultaneous induction of neurotoxic genes and repression of neurotrophic genes in astrocytes. Cover Image for this issue: doi: 10.1111/jnc.12564. © 2014 International Society for Neurochemistry.

publication date

  • January 1, 2014

published in

Digital Object Identifier (DOI)

start page

  • 932

end page

  • 939

volume

  • 129

issue

  • 6