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Sept 2011 - Institut de Recherche en Santé Mentale

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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

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