POSTMORTEM STUDY OF MESSENGER RNA EXPRESSION IN THE DORSOLATERAL PREFRONTAL CORTEX OF SUBJECTS WITH CONSUMMATE SUICIDE AND SUBSTANCE ABUSE

Autor: Fernando García-Dolores, AL Romero-Pimente, Mirna Morales, Roberto Cuauhtemoc Mendoza-Morales, Nancy Monroy, Consuelo Walss-Bass, Eli Elier González-Sáenz, Brenda Cabrera, Humberto Nicolini, Claudia Rangel, E Díaz-Otañes, A Mendoza-Larios
Rok vydání: 2019
Předmět:
Zdroj: European Neuropsychopharmacology. 29:S883
ISSN: 0924-977X
DOI: 10.1016/j.euroneuro.2017.08.185
Popis: Background It is estimated that subjects with alcohol abuse are almost 10 times more likely to commit suicide and those with substance abuse about 14 times more. The prefrontal cortex is the cerebral area responsible for decision making, inhibition and short-term memory, functions that have been altered in subjects with suicidal behavior. In addition, structural and functional changes in individuals with suicidal behavior have been identified in this area. Cognitive abilities associated with the prefrontal area, specifically the dorsolateral prefrontal cortex, have been identified in subjects with substance abuse. Therefore, it is of special interest to evaluate gene expression in this cerebral area in order to identify genes expressed in suicide subjects with substance use compared with suicide death without this comorbidity to have a better understanding of the pathology of suicide and that could be used in the future as biomarkers of suicidal behavior in subjects with substance abuse and implement adequate prevention measures for this sector of the population. Methods We collected samples from the dorsolateral prefrontal cortex of subjects who committed suicide and of subjects with death other than suicide. RNA isolation was performed using the Qiagen RNAeasy, after RNA extraction the purity of RNA extracted by means of spectrophotometry (NanoDrop1000 Spectrophotometer from Thermo Fisher) and its integrity with 1% agarose gel electrophoresis was evaluated. The expression of messenger RNA from 67 samples (43 Subjects with consummate suicide and 24 subjects with death other than suicide) through the HumanHT-12 v4 BeadChip microarray containing 47, 231 probes was evaluated. The analysis of the data obtained from the microarray will be performed comparing the expression of messenger RNA between the group with consummate suicide and the group with death other than suicide with a paired t-test for each probe evaluated in the microarray. Subsequently, a statistical model of ANOVA will be applied to assess whether the diagnosis of substance abuse during the lifetime and toxicology at the time of death had any effect on the expression of messenger RNA. The genes that are differentially expressed will be validated by real-time PCR. Results The final sample consisted of 67 brain samples divided into the group of "individuals who consumed suicide" (n=43) and the group of "controls" or subjects with a cause of death other than suicide (n=24). There were no significant differences in gender and age between both groups. The analysis of microarray data will be performed in the next weeks. Discussion Subjects with substance abuse are at increased risk for suicidal behavior, most studies of expression have excluded this group of patients and little is known about the molecular basis of the association between substance abuse and suicidal behavior. We hypothesize that subjects with death by self-harm and substance abuse have different expression profiles of the messenger RNA in the dorsolateral prefrontal cortex compared to suicide victims without substance abuse and controls who had a death from other causes. I believe that after conducting the analysis of the results of the microarray (which will take only a few weeks) we will be able to extend the discussion by commenting on the differences between the study groups.
Databáze: OpenAIRE
Externí odkaz: