PMID- 19926633
OWN - NLM
STAT- MEDLINE
DCOM- 20100222
LR  - 20141120
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 113
IP  - 2
DP  - 2010 Feb
TI  - Acute treatment with diphenyl diselenide inhibits glutamate uptake into rat 
      hippocampal slices and modifies glutamate transporters, SNAP-25, and GFAP 
      immunocontent.
PG  - 434-43
LID - 10.1093/toxsci/kfp282 [doi]
AB  - Diphenyl diselenide (PhSe)(2) is a selenium organic compound that has been 
      described to inhibit glutamate binding at synaptic membranes and uptake into 
      cortical slices, but there are no studies about its effects on glutamate 
      transporters and related synaptic proteins. Hippocampal slices from rats treated 
      acutely with (PhSe)(2) (1, 10, and 100 mg/kg, oral route) were evaluated on 
      glutamate uptake, redox state, the immunocontent of glial (glutamate/aspartate 
      transporter [GLAST] and glutamate transporter type I [GLT1]), neuronal 
      (excitatory amino acid carrier 1 [EAAC1]), and vesicular (vesicular glutamate 
      transporter 1 [VGLUT1]) glutamate transporters. Besides, cell viability was 
      evaluated by glial fibrillar acid protein (GFAP) and synaptosomal-associated 
      protein 25 (SNAP-25) immunocontent and 4', 6-diamidino-2-phenylindole (DAPI) and 
      Fluoro Jade C staining. Hippocampal slices from rats treated with (PhSe)(2) 
      exhibited a nondose-dependent inhibition of glutamate uptake (53, 38, and 45%, 
      respectively). All doses increased EAAC1, decreased SNAP-25, did not modify GLT1 
      immunocontent, and there was no evidence of oxidative stress. (PhSe)(2) (100 
      mg/kg) increased 32% GLAST, decreased 34% VGLUT1, and 21% GFAP immunocontent. 
      Besides, (PhSe)(2) (100 mg/kg) decreased by 25% GFAP-stained astrocytes and 27% 
      DAPI-stained cells in the CA1 subfield. Our results suggest that the increase of 
      EAAC1 and GLAST immunocontent by (PhSe)(2) might be a compensatory mechanism by 
      surviving cells in order to reduce extracellular glutamate levels, avoiding 
      possible neurotoxic effects. The impairment of glutamate uptake by the highest 
      dose of (PhSe)(2) seems to be related to a decrease on VGLUT1, SNAP-25, and 
      damage to astrocytes. Since there were no signs of oxidative stress, our findings 
      revealed that depending on the dose, acute administration of (PhSe)(2) causes 
      modifications in important synaptic-related proteins and damage to the 
      astrocytes, and these events must be taken into account in its pharmacological 
      properties.
FAU - Ardais, Ana P
AU  - Ardais AP
AD  - Laboratory of Studies on the Purinergic System, Post-Graduation Program in 
      Biological Sciences-Biochemistry, Department of Biochemistry, Health and Basic 
      Sciences Institute, Federal University of Rio Grande do Sul, Porto Alegre/RS, 
      Brazil.
FAU - Viola, Giordano G
AU  - Viola GG
FAU - Costa, Marcelo S
AU  - Costa MS
FAU - Nunes, Fernanda
AU  - Nunes F
FAU - Behr, Guilherme A
AU  - Behr GA
FAU - Klamt, Fabio
AU  - Klamt F
FAU - Moreira, Jose C F
AU  - Moreira JC
FAU - Souza, Diogo O
AU  - Souza DO
FAU - Rocha, Joao B T
AU  - Rocha JB
FAU - Porciuncula, Lisiane O
AU  - Porciuncula LO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091118
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Benzene Derivatives)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Organoselenium Compounds)
RN  - 0 (Synaptosomal-Associated Protein 25)
RN  - 0 (Vesicular Glutamate Transport Proteins)
RN  - 1666-13-3 (diphenyldiselenide)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Amino Acid Transport System X-AG/immunology/metabolism
MH  - Animals
MH  - Benzene Derivatives/*toxicity
MH  - Glial Fibrillary Acidic Protein/immunology/*metabolism
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/*metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - Organoselenium Compounds/*toxicity
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Synaptosomal-Associated Protein 25/immunology/*metabolism
MH  - Toxicity Tests, Acute
MH  - Vesicular Glutamate Transport Proteins/immunology/metabolism
EDAT- 2009/11/21 06:00
MHDA- 2010/02/23 06:00
CRDT- 2009/11/21 06:00
PHST- 2009/11/21 06:00 [entrez]
PHST- 2009/11/21 06:00 [pubmed]
PHST- 2010/02/23 06:00 [medline]
AID - kfp282 [pii]
AID - 10.1093/toxsci/kfp282 [doi]
PST - ppublish
SO  - Toxicol Sci. 2010 Feb;113(2):434-43. doi: 10.1093/toxsci/kfp282. Epub 2009 Nov 
      18.