- 作者: Youssef Sari; Anne L Prieto; Scott J Barton; Benjamin R Miller; George V Rebec
- 作者服務機構: Program in Neuroscience, Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
- 中文摘要: --
- 英文摘要:
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 β-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. - 中文關鍵字: --
- 英文關鍵字: --