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. 2008 Mar;33(2):131-41.

Serotonin receptor subtype and p11 mRNA expression in stress-relevant brain regions of suicide and control subjects

Hymie Anisman  1 , Lisheng Du, Mikos Palkovits, Gabor Faludi, Gabor G Kovacs, Peter Szontagh-Kishazi, Zul Merali, Michael O Poulter
Affiliations

Serotonin receptor subtype and p11 mRNA expression in stress-relevant brain regions of suicide and control subjects

Hymie Anisman et al. J Psychiatry Neurosci. 2008 Mar.

Abstract
in English, French

Objective: Studies comparing people suffering from depression who committed suicide with control subjects have yielded inconsistent results regarding serotonin (5-HT) involvement in pathology, possibly owing to procedural factors. Our objective was to investigate which 5-HT receptor subtypes might be associated with depression and suicide, whether receptor differences vary across brain regions and whether they are moderated by sex.

Methods: We assessed messenger ribonucleic acid (mRNA) expression of several 5-HT receptor subtypes and that of p11, a protein involved in the functional expression of 5-HT(1B), in several stress-relevant brain regions. Tissue was obtained soon after death, and RNA integrity and pH was confirmed to be appropriate. Brain tissue from suicide subjects suffering from depression and from control subjects who had died from other causes (10 men and 10 women in each condition) was obtained within 6.5 hours postmortem. Quantitative polymerase chain reaction analyses determined mRNA expression of 5-HT receptor subtypes and p11 within the frontopolar cortex, orbitofrontal cortex, hippocampus, amygdala and paraventricular nucleus. The 5-HT transporter (5-HTT) was also assessed in the raphe nucleus.

Results: Differences of 5-HT(1A), 5-HT(1B) and p11 mRNA expression between people who committed suicide and control subjects were relatively widespread, whereas 5-HT(2A) and 5-HT(2C) variations were restricted to the frontopolar cortex and amygdala. Within the dorsal raphe nucleus, neither 5-HT(1A) nor 5-HTT mRNA expression differed between those who committed suicide and control subjects.

Conclusion: Several 5-HT receptor subtypes are associated with depression and suicide, but these receptor differences vary across brain regions and are moderated by sex.

Objectif: Des études de comparaison entre des personnes atteintes de dépression qui se sont suicidées et des sujets témoins ont produit des résultats incohérents quant au rôle de la sérotonine (5-HT) dans la pathologie, peut-être à cause de facteurs liés à la façon de procéder. Nous voulions savoir quels sous-types de récepteurs de 5-HT pourraient être associés à la dépression et au suicide, si les différences au niveau des récepteurs varient entre les régions du cerveau et si elles sont modérées selon le sexe.

Méthodes: Nous avons évalué l'expression de l'acide ribonucléique messager (ARNm) de plusieurs sous-types de récepteurs de la 5-HT et de celui de la p11, protéine qui joue un rôle dans l'expression fonctionnelle de la 5-HT1B dans plusieurs régions du cerveau reliées au stress. Nous avons prélevé des tissus peu après le décès et confirmé l'intégrité de l'ARN et du pH. Moins de 6,5 h après la mort, on a prélevé du tissu cérébral de personnes suicidées atteintes de dépression et de sujets témoins morts d'autres causes (10 hommes et 10 femmes dans chaque cas). Des analyses quantitatives basées sur la réaction en chaîne de la polymérase ont déterminé l'expression de l'ARNm de sous-types de récepteurs de la 5-HT et de la p11 dans le cortex frontopolaire, le cortex orbitofrontal, l'hippocampe, les amygdales et le noyau paraventriculaire. On a aussi évalué les transporteurs de la 5-HT (5-HTT) dans le noyau de raphé.

Résultats: Les différences au niveau de l'expression de l'ARNm de la 5-HT1A, de la 5-HT1B et de la p11 entre les personnes qui se sont suicidées et les sujets témoins étaient relativement généralisées, tandis que les variations de la 5-HT2A et de la 5-HT2C étaient limitées au cortex frontopolaire et aux amygdales. Dans le noyau de raphé dorsal, il n'y a pas eu de différences au niveau de l'expression de l'ARNm de la 5-HT1A ou du 5-HTT entre les sujets qui se sont suicidés et les sujets témoins.

Conclusion: On associe plusieurs sous-types de récepteurs de la 5-HT à la dépression et au suicide, mais ces différences entre les récepteurs varient selon les régions du cerveau et sont modérées par le sexe.

Keywords: depression; receptors, serotonin; suicide.

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Figures

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Fig. 1: Mean (and standard error of the mean) messenger ribonucleic acid (mRNA) expression of 5-HT1A, 5-HT2A, 5-HT2C, 5-HT1B and p11 in the frontopolar cortex of suicide victims who suffered from depression and of control subjects. The left panel shows the data for men, and the right panel presents the data for women. Data are presented as normalized cycle thresholds (Ctn) wherein the expression of each species was normalized by subtracting its cycle threshold (Ct) from the synaptophysin Ct. Thus a negative Ctn indicates that the mRNA species was less abundant than that of synaptophysin. A change of 1 Ctn is equivalent to a 2-fold difference in the abundance of that species. *p < 0.05 relative to control subjects of the same sex.
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Fig. 2: Mean (and standard error of the mean) messenger ribonucleic acid expression of 5-HT1A, 5-HT2A, 5-HT2C, 5-HT1B and p11 in the orbital frontal cortex of of suicide victims who suffered from depression and of control subjects. The left panel shows the data for men, and the right panel presents the data for women. Data are presented as normalized cycle thresholds (Ctn) wherein the expression of each species was normalized by subtracting its cycle threshold (Ct) from the synaptophysin Ct. *p < 0.05 relative to control subjects of the same sex.
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Fig. 3: Mean (and standard error of the mean) messenger ribonucleic acid expression of 5-HT1A, 5-HT2A, 5-HT2C, 5-HT1B and p11 in the hippocampus of suicide victims who suffered from depression and of control subjects. The left panel shows the data for men, and the right panel presents the data for women. Data are presented as normalized cycle thresholds (Ctn) wherein the expression of each species was normalized by subtracting its cycle threshold (Ct) from the synaptophysin Ct.*p < 0.05 relative to control subjects of the same sex.
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Fig. 4: Mean (and standard error of the mean) messenger ribonucleic acid expression of 5-HT1A, 5-HT2A, 5-HT2C, 5-HT1B and p11 in the amygdala of suicide victims who suffered from depression and of control subjects. Because there were only a few samples from women, only the data from men are presented. Data are presented as normalized cycle thresholds (Ctn) wherein the expression of each species was normalized by subtracting its cycle threshold (Ct) from the synaptophysin Ct. *p < 0.05 relative to control subjects of the same sex.
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Fig. 5: Mean (and standard error of the mean) messenger ribonucleic acid expression of 5-HT1A, 5-HT2A, 5-HT2C, 5-HT1B and p11 in the paraventricular nucleus of the hypothalamus of suicide victims who suffered from depression and control subjects. The left panel shows the data for men, and the right panel presents the data for women. Data are presented as normalized cycle thresholds (Ctn) wherein the expression of each species was normalized by subtracting its cycle threshold (Ct) from the synaptophysin Ct. *p < 0.05 relative to control subjects of the same sex.
See this image and copyright information in PMC

References

    1. Biegon A, Israeli M. Regionally selective increases in beta-adrenergic receptor density in the brains of suicide victims. Brain Res 1988; 442: 199-203. - PubMed
    1. Drevets WC. Neuroimaging studies of mood disorders. Biol Psychiatry 2000;48:813-9. - PubMed
    1. Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 2001;11:240-9. - PubMed
    1. Dwivedi Y, Conley RR, Roberts RC, et al. [(3)H]cAMP binding sites and protein kinase a activity in the prefrontal cortex of suicide victims. Am J Psychiatry 2002;159:66-73. - PubMed
    1. Merali Z, Du L, Hrdina P, et al. Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical brain region. J Neurosci 2004;24:1478-85. - PMC - PubMed

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