ABSTRACT
Psychostimulants regulate behavioral responses in zebrafish via epigenetic mechanisms. We have previously shown that DNA methylation and histone deacetylase (HDAC) inhibition abolish nicotine-induced conditioned place preference (CPP) but little is known about the role of histone methylation in addictive-like behaviors. To assess the influence of histone methylation on nicotine-CPP, zebrafish were treated with a histone (H3) lysine-9 (K9) dimethyltransferase G9a/GLP inhibitor, BIX-01294 (BIX), which was administered before conditioning sessions. We observed a dual effect of the inhibitor BIX: at high doses inhibited while at low doses potentiated nicotine reward. Transcriptional expression of α6 and α7 subunits of the nicotinic acetylcholine receptor and of G9a, DNA methyl transferase-3, and HDAC-1 was upregulated in zebrafish with positive scores for nicotine-CPP. Changes in relative levels of these mRNA molecules reflected the effects of BIX on nicotine reward. BIX treatment per sé did not affect transcriptional levels of epigenetic enzymes that regulate trimethylation or demethylation of H3. BIX reduced H3K9me2 protein levels in a dose-dependent manner in key structures of the reward pathway. Thus, our findings indicated that different doses of BIX differentially affect nicotine CPP via strong or weak inhibition of G9a/GLP activity. Additionally, we found that the lysine demethylase inhibitor daminozide abolished nicotine-CPP and drug seeking. Our data demonstrate that H3 methylation catalyzed by G9a/GLP is involved in nicotine-CPP induction. Dimethylation of K9 at H3 is an important epigenetic modification that should be considered as a potential therapeutic target to treat nicotine reward and perhaps other drug addictions.
ABSTRACT
Este trabalho se propõe a analisar as relações existentes entre a presença de filho com deficiência intelectual e a oferta de trabalho materno no Brasil. A análise estratificou os resultados por grau de limitação decorrente da deficiência e por tipo de síndrome ou transtorno de desenvolvimento. Os dados são provenientes da Pesquisa Nacional de Saúde e foram utilizados modelos econométricos logit e tobit nas estimações. Os resultados sugerem uma redução média de 17 pontos percentuais na probabilidade de mães que tenham filho com deficiência intelectual estarem empregadas. Caso a deficiência provoque uma limitação intensa, a redução pode chegar a 25 pontos percentuais. Observou-se, ainda, que a deficiência intelectual do filho afeta de forma negativa e significativa o número de horas semanais de trabalho das mães que participam do mercado de trabalho, havendo uma redução média de 8,9 horas e, nos casos de limitação intensa, de 11,2 horas. Estes resultados podem ter implicações importantes na formulação de políticas públicas, uma vez que a deficiência intelectual do filho demonstra ser um entrave relevante para a participação das mães no mercado de trabalho.
This study aims to analyze the relationship between children's mental illness and mother's labor supply in Brazil. The analysis stratified results by the degree of limitation resulting from the disability and by type of syndromes or developmental disorders. Data come from the National Health Survey and Logit and Tobit econometric models were used in the estimations. Results suggest an average reduction of 17 percentage points in the probability of mother's work if they raise a child with intellectual disability and, if disability leads to severe limitation, the reduction may reach 25 percentage points. We also find that the child's intellectual disability negatively and significantly affects the number of weekly working hours for employed mothers, with an average reduction of 8.9 hours and, in cases of severe limitation, 11,2 hours. These results may have important implications for the formulation of public policies, since the child's intellectual disability proves to be a relevant obstacle to the participation of mothers in the labor market.
El objetivo de este trabajo es analizar la relación entre la presencia de hijos con discapacidad intelectual y la oferta de trabajo materno en Brasil. El análisis estratificó los resultados por el grado de limitación resultante de la discapacidad y por el tipo de síndromes o trastornos del desarrollo. Los datos provienen de la Encuesta Nacional de Salud y en las estimaciones se utilizaron modelos econométricos Logit y Tobit. Los resultados sugieren una reducción promedio de 17 puntos porcentuales en la probabilidad de que las madres que tienen hijos con discapacidad intelectual estén empleadas. Si la deficiencia causa una limitación intensa, la reducción puede alcanzar los 25 puntos porcentuales. También se observó que la discapacidad intelectual del niño afecta de manera negativa y significativa el número de horas semanales de trabajo de las madres que participan en el mercado laboral, con una reducción promedio de 8,9 horas y, en casos de limitación severa, de 11,2 horas. Estos resultados pueden tener implicaciones importantes para la formulación de políticas públicas, ya que la discapacidad intelectual del niño demuestra ser un obstáculo relevante para la participación de las madres en el mercado laboral.
