PMID- 20193040
OWN - NLM
STAT- MEDLINE
DCOM- 20100615
LR  - 20211020
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 113
IP  - 4
DP  - 2010 May
TI  - Increased expression of cholesterol 24S-hydroxylase results in disruption of 
      glial glutamate transporter EAAT2 association with lipid rafts: a potential role 
      in Alzheimer's disease.
PG  - 978-89
LID - 10.1111/j.1471-4159.2010.06661.x [doi]
AB  - The glial glutamate transporter EAAT2 (excitatory amino acid transporter 2) is 
      the major mediator of glutamate clearance that terminates glutamate-mediated 
      neurotransmission. Loss of EAAT2 and associated glutamate uptake function has 
      been reported in the brains of patients with Alzheimer's disease (AD). We 
      previously reported that EAAT2 is associated with lipid raft microdomains of the 
      plasma membrane. In the present study, we demonstrated that association of EAAT2 
      with lipid rafts is disrupted in AD brains. This abnormality is not a consequence 
      of neuron degeneration, oxidative stress, or amyloid beta toxicity. In AD brains, 
      cholesterol 24S-hydroxylase (CYP46), a key enzyme in maintenance of cholesterol 
      homeostasis in the brain, is markedly increased in astrocytes but decreased in 
      neurons. We demonstrated that increased expression of CYP46 in primary astrocytes 
      results in a reduction of membrane cholesterol levels and leads to the 
      dissociation of EAAT2 from lipid rafts and the loss of EAAT2 and associated 
      glutamate uptake function. These results suggest that a disturbance of 
      cholesterol metabolism may contribute to loss of EAAT2 in AD.
FAU - Tian, Guilian
AU  - Tian G
AD  - Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, USA.
FAU - Kong, Qiongman
AU  - Kong Q
FAU - Lai, Liching
AU  - Lai L
FAU - Ray-Chaudhury, Abhik
AU  - Ray-Chaudhury A
FAU - Lin, Chien-liang G
AU  - Lin CL
LA  - eng
GR  - R01 MH059805/MH/NIMH NIH HHS/United States
GR  - MH59805/MH/NIMH NIH HHS/United States
GR  - R01 MH059805-06/MH/NIMH NIH HHS/United States
GR  - R01 NS064275/NS/NINDS NIH HHS/United States
GR  - R01 NS064275-01A1/NS/NINDS NIH HHS/United States
GR  - NS64275/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100227
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.14.25 (Cholesterol 24-Hydroxylase)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*metabolism/physiopathology
MH  - Astrocytes/*metabolism
MH  - Brain/*metabolism/physiopathology
MH  - Brain Chemistry/physiology
MH  - Cholesterol/metabolism
MH  - Cholesterol 24-Hydroxylase
MH  - Excitatory Amino Acid Transporter 2/*metabolism
MH  - Glutamic Acid/metabolism
MH  - Humans
MH  - Membrane Microdomains/*metabolism
MH  - Steroid Hydroxylases/*metabolism
MH  - Up-Regulation/physiology
PMC - PMC3010752
MID - NIHMS186827
EDAT- 2010/03/03 06:00
MHDA- 2010/06/16 06:00
PMCR- 2011/05/01
CRDT- 2010/03/03 06:00
PHST- 2010/03/03 06:00 [entrez]
PHST- 2010/03/03 06:00 [pubmed]
PHST- 2010/06/16 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - JNC6661 [pii]
AID - 10.1111/j.1471-4159.2010.06661.x [doi]
PST - ppublish
SO  - J Neurochem. 2010 May;113(4):978-89. doi: 10.1111/j.1471-4159.2010.06661.x. Epub 
      2010 Feb 27.