TY - JOUR
T1 - Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS
AU - Regan, Melissa R.
AU - Huang, Yanhua H.
AU - Yu, Shin Kim
AU - Dykes-Hoberg, Margaret I.
AU - Jin, Lin
AU - Watkins, Andrew M.
AU - Bergles, Dwight E.
AU - Rothstein, Jeffrey D.
PY - 2007/6/20
Y1 - 2007/6/20
N2 - Glutamate transporters regulate excitatory neurotransmission and prevent glutamate-mediated excitotoxicity in the CNS. To better study the cellular and temporal dynamics of the expression of these transporters, we generated bacterial artificial chromosome promoter Discosoma red [glutamate-aspartate transporter (GLAST)] and green fluorescent protein [glutamate transporter-1 (GLT-1)] reporter transgenic mice. Analysis of these mice revealed a differential activation of the transporter promoters not previously appreciated. GLT-1 promoter activity in the adult CNS is almost completely restricted to astrocytes, often and unexpectedly in a nonoverlapping pattern with GLAST. Spinal cord GLT-1 promoter reporter, protein density, and physiology were 10-fold lower than in brain, suggesting a possible mechanism for regional sensitivity seen in disease. The GLAST promoter is active in both radial glia and many astrocytes in the developing CNS but is downregulated in most astrocytes as the mice mature. In the adult CNS, the highest GLAST promoter activity was observed in radial glia, such as those located in the subgranular layer of the dentate gyrus. The continued expression of GLAST by these neural progenitors raises the possibility that GLAST may have an unanticipated role in regulating their behavior. In addition, GLAST promoter activation was observed in oligodendrocytes in white matter throughout many (e.g., spinal cord and corpus callosum), but not all (e.g., cerebellum), CNS fiber tracts. Overall, these studies of GLT-1 and GLAST promoter activity, protein expression, and glutamate uptake revealed a close correlation between transgenic reporter signals and uptake capacity, indicating that these mice provide the means to monitor the expression and regulation of glutamate transporters in situ.
AB - Glutamate transporters regulate excitatory neurotransmission and prevent glutamate-mediated excitotoxicity in the CNS. To better study the cellular and temporal dynamics of the expression of these transporters, we generated bacterial artificial chromosome promoter Discosoma red [glutamate-aspartate transporter (GLAST)] and green fluorescent protein [glutamate transporter-1 (GLT-1)] reporter transgenic mice. Analysis of these mice revealed a differential activation of the transporter promoters not previously appreciated. GLT-1 promoter activity in the adult CNS is almost completely restricted to astrocytes, often and unexpectedly in a nonoverlapping pattern with GLAST. Spinal cord GLT-1 promoter reporter, protein density, and physiology were 10-fold lower than in brain, suggesting a possible mechanism for regional sensitivity seen in disease. The GLAST promoter is active in both radial glia and many astrocytes in the developing CNS but is downregulated in most astrocytes as the mice mature. In the adult CNS, the highest GLAST promoter activity was observed in radial glia, such as those located in the subgranular layer of the dentate gyrus. The continued expression of GLAST by these neural progenitors raises the possibility that GLAST may have an unanticipated role in regulating their behavior. In addition, GLAST promoter activation was observed in oligodendrocytes in white matter throughout many (e.g., spinal cord and corpus callosum), but not all (e.g., cerebellum), CNS fiber tracts. Overall, these studies of GLT-1 and GLAST promoter activity, protein expression, and glutamate uptake revealed a close correlation between transgenic reporter signals and uptake capacity, indicating that these mice provide the means to monitor the expression and regulation of glutamate transporters in situ.
KW - Astroglia
KW - BAC
KW - GLAST
KW - GLT-1
KW - Glutamate
KW - Membrane
KW - Oligodendroglial
KW - Transgenic
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UR - http://www.scopus.com/inward/citedby.url?scp=34250870091&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0790-07.2007
DO - 10.1523/JNEUROSCI.0790-07.2007
M3 - Article
C2 - 17581948
AN - SCOPUS:34250870091
SN - 0270-6474
VL - 27
SP - 6607
EP - 6619
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 25
ER -