PMID- 22728822
OWN - NLM
STAT- MEDLINE
DCOM- 20121105
LR  - 20201209
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 522
IP  - 2
DP  - 2012 Aug 1
TI  - Cognitive dysfunction and glutamate reuptake: effect of EAAT2 polymorphism in 
      schizophrenia.
PG  - 151-5
LID - 10.1016/j.neulet.2012.06.030 [doi]
AB  - A disturbance of glutamatergic transmission has been suggested to contribute to 
      the development of schizophrenic pathophysiology, based primarily on the ability 
      of glutamate receptor antagonists to induce schizophrenic-like symptoms. The 
      excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of 
      glutamate uptake. It also contributes to energy metabolism in the brain, by 
      transporting glutamate into astrocytes for conversion into glutamine. A 
      dysregulation of its level of expression has been associated with multiple 
      neurological disorders. Blocking glutamate uptake by EAAT2 in cultured 
      oligodendrocytes leads to cell death, demyelination and axonal damage, suggesting 
      that it is crucial for normal oligodendrocyte function. Different studies focused 
      on EAAT2 alterations among subjects affected by schizophrenia, reporting a 
      decreased expression in the parahippocampal region and in the dorsolateral 
      prefrontal cortex. Moreover, subjects with the high-risk metabotropic glutamate 
      receptor 3 (GRM3) haplotype associated with schizophrenia had lower EAAT2 
      expression in the prefrontal cortex and also showed impaired cognitive 
      performances for measures of verbal list learning and verbal fluency. EAAT2 
      protein activity is regulated by a SNP rs4354668 (-181T/G) which falls in the 
      gene promoter region, with the G allele resulting in a lower activity of the 
      transporter. Based on these data, we assessed possible effects of the -181T/G 
      EAAT2 polymorphism on two core prefrontal cognitive performances, known to be 
      impaired in schizophrenia, in a sample of 211 clinically stabilized patients. We 
      observed better executive functions (WCST, no. of categories) and working memory 
      (N-back: 1-back, 2-back) performances in subjects homozygous for the T allele, 
      compared to the G carriers group. These observations suggest that the presence of 
      the G allele is associated, among patients with schizophrenia, with a 
      disadvantageous effect on core cognitive functions that depend on prefrontal 
      cortex activity. These results are preliminary and need to be replicated by 
      future and larger studies, however they suggest that EAAT2 inefficiency may 
      represent a target of interest for development of pharmacological strategies 
      aimed to improve prefrontal performances by compensating the impaired glutamate 
      reuptake.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Spangaro, Marco
AU  - Spangaro M
AD  - San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, 
      Italy.
FAU - Bosia, Marta
AU  - Bosia M
FAU - Zanoletti, Andrea
AU  - Zanoletti A
FAU - Bechi, Margherita
AU  - Bechi M
FAU - Cocchi, Federica
AU  - Cocchi F
FAU - Pirovano, Adele
AU  - Pirovano A
FAU - Lorenzi, Cristina
AU  - Lorenzi C
FAU - Bramanti, Placido
AU  - Bramanti P
FAU - Benedetti, Francesco
AU  - Benedetti F
FAU - Smeraldi, Enrico
AU  - Smeraldi E
FAU - Cavallaro, Roberto
AU  - Cavallaro R
LA  - eng
PT  - Journal Article
DEP - 20120621
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Glutamate Plasma Membrane Transport Proteins)
RN  - 0 (SLC1A2 protein, human)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cognition Disorders/*genetics
MH  - Excitatory Amino Acid Transporter 2
MH  - Female
MH  - Glutamate Plasma Membrane Transport Proteins/*genetics/metabolism
MH  - Glutamic Acid/*metabolism
MH  - Humans
MH  - Male
MH  - Memory, Short-Term
MH  - Middle Aged
MH  - Polymorphism, Genetic
MH  - Prefrontal Cortex/*metabolism
MH  - Schizophrenia/*genetics/metabolism
MH  - *Schizophrenic Psychology
MH  - Young Adult
EDAT- 2012/06/26 06:00
MHDA- 2012/11/06 06:00
CRDT- 2012/06/26 06:00
PHST- 2012/04/23 00:00 [received]
PHST- 2012/06/09 00:00 [revised]
PHST- 2012/06/11 00:00 [accepted]
PHST- 2012/06/26 06:00 [entrez]
PHST- 2012/06/26 06:00 [pubmed]
PHST- 2012/11/06 06:00 [medline]
AID - S0304-3940(12)00828-2 [pii]
AID - 10.1016/j.neulet.2012.06.030 [doi]
PST - ppublish
SO  - Neurosci Lett. 2012 Aug 1;522(2):151-5. doi: 10.1016/j.neulet.2012.06.030. Epub 
      2012 Jun 21.