TAILIEUCHUNG - Ceftriaxone-induced up-regulation of cortical and striatal GLT1 in the R6/2 model of Huntington’s disease

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by cortico-striatal dysfunction and loss of glutamate uptake. At 7 weeks of age, R6/2 mice, which model an aggressive form of juvenile HD, show a glutamate-uptake deficit in striatum that can be reversed by treatment with ceftriaxone, a b-lactam antibiotic that increases GLT1 expression. Only at advanced ages ( 11 weeks), however, do R6/2 mice show an actual loss of striatal GLT1. Here, we tested whether ceftriaxone can reverse the decline in GLT1 expression that occurs in older R6/2s. Results: Western blots were used to assess GLT1 expression in both striatum. | Sari et al. Journal of Biomedical Science 2010 17 62 http content 17 1 62 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Ceftriaxone-induced up-regulation of cortical and striatal GLT1 in the R6 2 model of Huntington s disease I 11 1 2 3 A I Dzi 1 2 c I D 1 2 ID l I I I I ì 1 2 4 r m ị r r 1 2 Yousser sari Anne L rrieto Scott J Barton Benjamin R Miller George V Rebec Abstract Background Huntington s disease HD is an inherited neurodegenerative disorder characterized by cortico-striatal dysfunction and loss of glutamate uptake. At 7 weeks of age R6 2 mice which model an aggressive form of juvenile HD show a glutamate-uptake deficit in striatum that can be reversed by treatment with ceftriaxone a p-lactam antibiotic that increases GLT1 expression. Only at advanced ages 11 weeks however do R6 2 mice show an actual loss of striatal GLT1. Here we tested whether ceftriaxone can reverse the decline in GLT1 expression that occurs in older R6 2s. Results Western blots were used to assess GLT1 expression in both striatum and cerebral cortex in R6 2 and corresponding wild-type WT mice at 9 and 13 weeks of age. Mice were euthanized for immunoblotting 24 hr after five consecutive days of once daily injections ip of ceftriaxone 200 mg kg or saline vehicle. Despite a significant GLT1 reduction in saline-treated R6 2 mice relative to WT at 13 but not 9 weeks of age ceftriaxone treatment increased cortical and striatal GLT1 expression relative to saline in all tested mice. Conclusions The ability of ceftriaxone to up-regulate GLT1 in R6 2 mice at an age when GLT1 expression is significantly reduced suggests that the mechanism for increasing GLT1 expression is still functional. Thus ceftriaxone could be effective in modulating glutamate transmission even in late-stage HD. Background Ample evidence indicates that the neuropathology associated with .

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