Sept 2011 - Institut de Recherche en Santé Mentale
Sept 2011 - Institut de Recherche en Santé Mentale
Sept 2011 - Institut de Recherche en Santé Mentale
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
Table 1. Postmortem Brains. Prefrontal cortex brain tissue (BA44) was obtained in collaboration<br />
with the Quebec Coroner’s Office from the Quebec Suici<strong>de</strong> Brain Bank (QSBB). All individuals were<br />
male and groups were matched for age, pH and PMI. Psychological autopsies were performed postmortem<br />
for both cases (n=15) and controls (n=15) based on DSM-IV criteria. The control group had<br />
no history of suicidal behaviour or major mood or psychotic disor<strong>de</strong>rs.<br />
RESEARCH POSTER PRESENTATION DESIGN © <strong>2011</strong><br />
www.PosterPres<strong>en</strong>tations.com<br />
A. B.<br />
SAT1<br />
2.5<br />
2.5<br />
2.0<br />
2.0<br />
1.5<br />
1.5<br />
1.0<br />
1.0<br />
0.5<br />
0.5<br />
0.0<br />
0.0<br />
Controls<br />
Suici<strong>de</strong>s<br />
Figure 2. Expression of SAT1 and SMOX. Brain expression of SAT1 and SMOX g<strong>en</strong>es(BA44). (A)<br />
SAT1. Group mean ± SEM of AQ values from qRT-PCR (Normalized to GAPDH). SAT1 showed a<br />
significant down-regulation in suici<strong>de</strong> completers (**P0.05,<br />
Pearsons r = -0.27, R"=0.07).(C) SAT1 vs. miR-34c-5p (p0.05, Pearsons r = -0.11, R"=0.01). (D)<br />
SAT1 vs. miR-320c (p"L,(.)4)*7"C0D9=="8,9K*+(9)>7"C',)+*-=7"M4*N*0":-,-G-"<br />
1234567831520<br />
=>3@0W0=A5X0Y;2;0;XE4;==1520<br />
4;=7?3=0<br />
4;=7?3=0<br />
•!Suici<strong>de</strong> is a major public health problem. It is estimated that suici<strong>de</strong><br />
accounts for 1.8% of the total <strong>de</strong>aths in the United States [1]. Over<br />
the last <strong>de</strong>ca<strong>de</strong>s, a large body of evi<strong>de</strong>nce has shown that individuals<br />
who commit suici<strong>de</strong> have a predisposition that is mediated by<br />
neurobiological factors [2].<br />
•!Changes in the expression of polyamine metabolic <strong>en</strong>zymes have<br />
be<strong>en</strong> observed in multiple psychiatric conditions, and we have<br />
previously shown the expression of the polyamine g<strong>en</strong>es SAT1 and<br />
SMOX to be down regulated in the brains of suici<strong>de</strong> completers [3].<br />
•!MicroRNAs (miRNAs) are small non-coding RNAs that regulate g<strong>en</strong>e<br />
expression by means of binding to complem<strong>en</strong>tary sequ<strong>en</strong>ces usually<br />
located in the 3 untranslated region (UTR) of a target g<strong>en</strong>e,<br />
g<strong>en</strong>erally leading to mRNA <strong>de</strong>gradation or translational repression [4].<br />
A growing body of evi<strong>de</strong>nce supports the role of miRNAs in<br />
neuropsychiatric disor<strong>de</strong>rs such as schizophr<strong>en</strong>ia and bipolar disor<strong>de</strong>r<br />
[5].<br />
•!We hypothesize that the down-regulation of the SAT1 and SMOX<br />
g<strong>en</strong>es in suici<strong>de</strong> completers could be influ<strong>en</strong>ced by miRNA posttranscriptional<br />
regulation.!<br />
59:;831)%0 VA/U"W"#/@" VX/#"W"A/X"<br />
EA10 #A/V"W"%/@" V@/@"W"X/V"<br />
9&+,'0!B0 X/U"W"$/$2" X/X"W"$/$U"<br />
Qty Mean (SAT1/GAPDH)<br />
Qty Mean<br />
**<br />
**<br />
8>2616>3;0*,42>#0<br />
SAT1 3’UTR<br />
SMOX 3’UTR<br />
*<br />
Qty Mean (SMOX/GAPDH)<br />
4;=7?3=0<br />
* **<br />
**<br />
Qty Mean (miR-139-5p/RNU6B)<br />
Qty Mean (miR-34c-5p/RNU6B)<br />
Qty Mean (miR-139-5p)<br />
Qty Mean (miR-34c-5p)<br />
Qty Mean (miR-139-5p)<br />
Qty Mean (miR-34c-5p)<br />
**<br />
*<br />
Qty Mean (miR-320c/RNU6B)<br />
Qty Mean (miR-195/RNU6B)<br />
=>3@0<br />
Qty Mean (miR-195)<br />
Qty Mean (miR-320c)<br />
=A5X0<br />
Qty Mean (miR-195)<br />
Qty Mean (miR-320c)<br />
*<br />
**<br />
ID<br />
miRNA Sequ<strong>en</strong>ce<br />
M#+N*,4N@OPNQ!00 """U["487>8>Y7I0-0I4I40400-I"V["<br />
M#+N*,4NOR/NQ!0 """U["-YY8>Y7YI4-I44-I04I-44I0"V[""<br />
M#+N*,4N@PQ0 """U["4>Y8>Y8>0-I---4-44II0"V["<br />
M#+N*,4NOTU/0 """U["->>>Y87YII44I-I-III4"V["<br />
microRNA<br />
Polyamine G<strong>en</strong>es<br />
SAT1<br />
miR-139-5p<br />
SMOX<br />
miR-195<br />
OAZ1<br />
miR-34c-5p<br />
OAZ2<br />
miR-320c<br />
AMD1<br />
ARG2<br />
SMS<br />
8528?7=152=0<br />
1. We found a significant up-regulation of miRNAs<br />
predicted to target the 3UTR of SAT1 and SMOX in the<br />
brains of suici<strong>de</strong> completers compared to controls.<br />
2. We <strong>de</strong>monstrated a significant negative correlation in<br />
expression betwe<strong>en</strong> SAT1, miR-320c and miR-34c-5p, and<br />
betwe<strong>en</strong> SMOX, miR-320c and miR-139-5p.<br />
3. Our results suggest a relationship betwe<strong>en</strong> these 4<br />
miRNAs and the polyamine g<strong>en</strong>es SAT1 and SMOX in suici<strong>de</strong><br />
behavior and we postulate that the down-regulation of<br />
SAT1 and SMOX is post-transcriptionally regulated by miRNA<br />
activity.<br />
4;Z;4;28;=0<br />
>8I25[?;6YA;23=0<br />
miR-124a<br />
miR-497<br />
miR-873<br />
miR-139-5p<br />
miR-195<br />
miR-34a<br />
miR-198<br />
miR-34c-5p<br />
miR-320c<br />
" "<br />
"""" " " " "<br />
"""" 0<br />
www.theroyal.ca 4