Estudo translacional sobre a qualidade do cuidado materno em resposta ao estresse neonatal, sua associação com ansiedade na vida adulta e investigação de potenciais mecanismos envolvidos

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

2011

RESUMO

Introduction: In humans, there is the suggestion that an adverse early life environment is related to the development of anxiety disorders in adulthood. This association could potentially be mediated by stress responses, brain-derived neurotrophic factor (BDNF) and by neuronal nitric oxide synthase (nNOS). This study aimed at proposing an animal model for the development of adult anxiety-like behavior, using as intervention an adverse early life environment affecting matenal care, and verifies potencial mechanisms related to the development of anxiety-like behavior. Another aim was investigate similar associations in humans. Methodology: By the second day of life, litters of Wistar rats and their dams where divided in two groups: intervention, with limited access to nesting material, or control. Maternal behavior was observed from day 1 to day 9 of life. After weaning, animals¿ weight and standard chow consumption were measured once a week. Starting on day 60 of life, rats were submitted to behavioral testing. Glucose and lipid profile were assessed. Plasma, hippocampus, amygdala and periaqueductal gray BDNF contents and hippocampus nitric oxide were also measured. A subgroup of naive animals was submitted to restraint stress for determination of corticosterone curve. In humans, 129 adolescents, screened for anxiety using the Screen for Children and Anxiety Related Emotional Disorders (SCARED) scale, responded to the Parental Bonding Instrument (PBI), collected blood for BDNF measurements and were genotyped for BDNF Val66Met polymorphism. Results: Intervention dams showed increased contact of low quality with their pups when compared to control dams. The intervention group consumed less standard chow than the control group. No differences in body weight gain, acute palatable food consumption, rebound hyperphagia and open field test were observed between groups. On plus maze test, the intervention was associated with higher anxiety-like behavior, however differently between the sexes. Higher plasma BDNF levels were found in the intervention group and low quality maternal care (pure contact) was positively correlated with adult peripheral BDNF. There were no differences in hippocampus, amygdala and periaqueductal gray BDNF contents, as hippocampus nitric oxide contents. Males of the intervention group took longer to reach the corticosterone peak. In humans, negative correlations between maternal care and anxiety symptoms were observed, as well as a positive correlation between overprotection and serum BDNF levels only among the Met carriers. Conclusion: The animal model proposed showed that an early life stress, able to alter the relationship between dam and pup, have a persistent impact on anxiety-like behavior and peripheral BDNF levels. These findings were similar to the associations described in humans. The translational approach to the question evidenced that the effects of early trauma may be mediated through maternal care, being the increased peripheral BDNF a potential relevant marker for these individuals.

ASSUNTO(S)

comportamento materno maternal behavior anxiety ansiedade brain-derived neurotrophic factor fator neurotrófico derivado do encéfalo

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