PMID- 20401690
OWN - NLM
STAT- MEDLINE
DCOM- 20100907
LR  - 20211020
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 35
IP  - 8
DP  - 2010 Aug
TI  - Glycolysis inhibition decreases the levels of glutamate transporters and enhances 
      glutamate neurotoxicity in the R6/2 Huntington's disease mice.
PG  - 1156-63
LID - 10.1007/s11064-010-0168-5 [doi]
AB  - Excitotoxicity has been associated with the loss of medium spiny neurons (MSN) in 
      Huntington's disease (HD). We have previously observed that the content of the 
      glial glutamate transporters, glutamate transporter 1 (GLT-1) and 
      glutamate-aspartate transporter (GLAST), diminishes in R6/2 mice at 14 weeks of 
      age but not at 10 weeks, and that this change correlates with an increased 
      vulnerability of striatal neurons to glutamate toxicity. We have also reported 
      that inhibition of the glycolytic pathway decreases glutamate uptake and enhances 
      glutamate neurotoxicity in the rat brain. We now show that at 10-weeks of age, 
      glutamate excitotoxicity is precipitated in R6/2 mice, after the treatment with 
      iodoacetate (IOA), an inhibitor of the glycolytic enzyme, 
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). IOA induces a larger inhibition 
      of GAPDH in R6/2 mice, while it similarly reduces the levels of GLT-1 and GLAST 
      in wild-type and transgenic animals. Results suggest that metabolic failure and 
      altered glutamate uptake are involved in the vulnerability of striatal neurons to 
      glutamate excitotoxicity in HD.
FAU - Estrada-Sanchez, Ana Maria
AU  - Estrada-Sanchez AM
AD  - Departamento de Neuropatologia Molecular, Division de Neurociencias, Instituto de 
      Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico DF, Mexico.
FAU - Montiel, Teresa
AU  - Montiel T
FAU - Massieu, Lourdes
AU  - Massieu L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100418
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Iodoacetates)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 1.2.1.12 (Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating))
SB  - IM
MH  - Amino Acid Transport System X-AG/*metabolism
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Female
MH  - Glutamic Acid/*metabolism/toxicity
MH  - Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/antagonists & 
      inhibitors/metabolism
MH  - Glycolysis
MH  - Huntington Disease/genetics/*metabolism
MH  - Iodoacetates/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
EDAT- 2010/04/20 06:00
MHDA- 2010/09/08 06:00
CRDT- 2010/04/20 06:00
PHST- 2010/02/17 00:00 [received]
PHST- 2010/04/02 00:00 [accepted]
PHST- 2010/04/20 06:00 [entrez]
PHST- 2010/04/20 06:00 [pubmed]
PHST- 2010/09/08 06:00 [medline]
AID - 10.1007/s11064-010-0168-5 [doi]
PST - ppublish
SO  - Neurochem Res. 2010 Aug;35(8):1156-63. doi: 10.1007/s11064-010-0168-5. Epub 2010 
      Apr 18.