Transcriptional profiling of striatal neurons in response to single or concurrent activation of dopamine D2, adenosine A(2A) and metabotropic glutamate type 5 receptors: focus on beta-synuclein expression.
G protein-coupled receptor oligomerization is a concept which is changing the understanding of classical pharmacology. Both, oligomerization and functional interaction between adenosine A(2A,) dopamine D(2) and metabotropic glutamate type 5 receptors have been demonstrated in the striatum. However, the transcriptional consequences of receptors co-activation are still unexplored. We aim here to determine the changes in gene expression of striatal primary cultured neurons upon isolated or simultaneous receptor activation. Interestingly, we found that 95 genes of the total analyzed (15,866 transcripts and variants) changed their expression in response to simultaneous stimulation of all three receptors. Among these genes, we focused on the β-synuclein (β-Syn) gene (SCNB). Quantitative PCR verified the magnitude and direction of change in expression of SCNB. Since β-Syn belongs to the homologous synuclein family and may be considered a natural regulator of α-synuclein (α-Syn), it has been proposed that β-Syn might act protectively against α-Syn neuropathology.
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain.
Laia
L
Canela
Elisabet
E
Selga
Juan Manuel
JM
García-Martínez
Olavo B
OB
Amaral
Víctor
V
Fernández-Dueñas
Jordi
J
Alberch
Enric I
EI
Canela
Rafael
R
Franco
Véronique
V
Noé
Carme
C
Lluís
Carlos J
CJ
Ciudad
Francisco
F
Ciruela
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D051846:beta-Synuclein / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2; D018094:Receptors, Metabotropic Glutamate; D051844:alpha-Synuclein; D051846:beta-Synuclein