Early life genetic, epigenetic and environmental factors shaping emotionality in rodents

Holmes, Andrew; Guisquet, A.M. Le; Vogel, Elise; Millstein, Rachel; Leman, Samuel; Belzung, Catherine

doi:10.1016/j.neubiorev.2005.04.012

Cited by 268 publications

(189 citation statements)

References 183 publications

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“…In humans, exposure to stress or trauma, especially during childhood, is linked with increased risk for a variety of psychiatric disorders, including anxiety disorders and depression (Charney and Manji, 2004;Hammen, 2005;Heim et al, 2010). Similar findings have been observed in animal models of early-life stress (de Kloet et al, 2005;Holmes et al, 2005). Further, the effects of early-life stress may interact with heritable variation in serotonergic genes to shape individual differences in anxiety and depression risk.…”

Section: Introductionmentioning

confidence: 55%

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Donaldson

Piel

Santos

et al. 2013

Neuropsychopharmacol

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The serotonin 1A receptor (5-HT1A) has a major role in modulating the effects of serotonin on mood and behavior. Previous studies have shown that knockout of 5-HT1A selectively in the raphe leads to higher levels of anxiety during adulthood. However, it remains unclear whether this phenotype is due to variation in receptor levels specifically during development or throughout life. To test the hypothesis that developmental sensitivity may underlie the effects of 5-HT1A on anxiety, we used an inducible transgenic system to selectively suppress 5-HT1A levels in serotonergic raphe neurons from post-natal days (P) 14 to P30, with a maximal reduction of 40% at P21 and return to regular levels by P30. This developmental decrease in receptor levels has long-lasting consequences, increasing anxiety and decreasing social investigation in adulthood. In addition, post-natal knockdown of autoreceptors leads to long-term increases in the excitability of serotonergic neurons, which may represent a mechanism underlying the effects of post-natal receptor variation on behavior later in life. Finally, we also examined the interplay between receptor variation and juvenile exposure to stress (applied from P14 to P21). Similar to receptor knockdown, juvenile exposure to stress led to increased anxiety phenotypes but did not exacerbate 5-HT1A knockdown-mediated anxiety levels. This work indicates that the effects of 5-HT1A autoreceptors on anxiety and social behaviors are developmentally mediated and suggests that natural variations in the expression of 5-HT1A may act during development to influence individual anxiety levels and contribute to susceptibility to anxiety disorders.

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Section: Introductionmentioning

confidence: 55%

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Donaldson

Piel

Santos

et al. 2013

Neuropsychopharmacol

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“…Recent findings also demonstrate that adolescent mice of different strains may vary in their anxiety-related responses to certain environmental manipulations. For example, A/J mice housed with C57BL/ 6J mice during adolescence subsequently exhibited lower levels of anxiety-like behavior in adulthood as compared to A/J mice housed with conspecifics from the same strain while, in contrast, anxiety-like behaviors in C57BL/6J mice were unaffected by social housing conditions [22]. These data suggest that the ontogeny of anxiety-and possibly other 'emotionrelated' behaviors may vary across genetic backgrounds, and that a comparison of adolescents versus adults in different mouse strains, both inbred and outbred, may yield valuable insights.…”

Section: Discussionmentioning

confidence: 99%

“…Another potentially critical variable influencing these behaviors and other is genetic background of mice tested. Mouse strains are well known to differ on various measures anxiety-and depression-related behavior and stress reactivity (for recent review, see [22]). Recent findings also demonstrate that adolescent mice of different strains may vary in their anxiety-related responses to certain environmental manipulations.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice

Hefner¹,

Holmes²

2007

Behavioural Brain Research

168

123

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Adolescence is characterized by behavioral traits such as emotional lability and impulsivity that are associated with increased vulnerability to affective illness and addictions. Research in rodents has found that adolescent rats and mice differ from adults on measures of anxiety-like behavior, noveltyseeking and stress-responsivity. The present study sought to extend these data by evaluating fear-, anxiety-and depression-related behaviors in male C57BL/6J mice aged four (early adolescent), six (peri-adolescent) or eight (early adult) weeks of age. Age-groups were compared on: Pavlovian fear conditioning and extinction, anxiety-like behavior and exploratory locomotion (using elevated plusmaze and novel open field), and depression-related behavior (via forced swim test). Results showed that early adolescent mice exhibited enhanced fear conditioning, but extinguished at a similar rate as adults. There were no major differences in anxiety-like behavior across age-groups, although early adolescent and peri-adolescent mice exhibited less exploratory locomotion than adults. Depressionrelated immobility behavior in the forced swim test was lower in early adolescents than adult mice across three test exposures. Present findings in the C57BL/6J inbred strain add to growing evidence of changes in rodent fear-and stress-related behaviors across the developmental transition from juvenility through adulthood. Understanding the neural basis of these ontogenic changes could provide insight into factors could provide insight into the pathogenesis and treatment of affective disorders that have their origins in adolescence.

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“…Champagne, 2008;Fagiolini, Jensen, & Champagne, 2009;Franklin, Saab, & Mansuy, 2012;Holmes et al, 2005;Muhammad & Kolb, 2011), tem mostrado que determinados eventos ambientais, especialmente aqueles ocorridos nos primeiros anos de vida, estão consistentemente relacionadas com alterações epigenéticas e podem ser transmitidos para a geração seguinte. Os mecanismos epigenéticos foram definidos por Gudsnuk e Champagne (2011) como alterações moleculares no DNA em si ou nas proteínas as quais o DNA está estreitamente ligado e podem ser induzidas por eventos ambientais.…”

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“…Assim, diferenças em cuidados maternais estão relacionadas com a saúde de seus fi lhos. Tem-se considerado que este efeito ocorre, pelo menos em parte, mediado pelas infl uências dos comportamentos de cuidados maternais no desenvolvimento dos sistemas neurais subjacentes a respostas ao estresse 1 , sejam respostas comportamentais ou endócrinas (De Bellis et al, 1994;Caldji et al, 2000;Coplan et al, 1996;Francis & Meaney, 1999;Franklin et al, 2012;Higley, Haser, Suomi, & Linnoila, 1991;Holmes et al, 2005;Meaney et al, 1996;Seckl & Meaney, 1994;Weiss, Pryce, Jongen-Relo, Nanz-Bahr, & Feldon, 2004).…”

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Epigenética, Cuidados Maternais e Vulnerabilidade ao Estresse: Conceitos Básicos e Aplicabilidade

Noro¹,

Gon²

2015

Psicol. Reflex. Crit.

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ResumoCuidados maternais são experiências do início da vida que têm sido consistentemente relacionados com alterações na expressão gênica por meio de mecanismos epigenéticos como a metilação do DNA ou a modifi cação de suas histonas. O objetivo deste trabalho é apresentar uma investigação teórica sobre cuidados maternais enquanto evento ambiental que pode produzir alterações epigené-ticas atuantes na composição da vulnerabilidade ao estresse. A investigação teve por base estudos empíricos e de revisão de literatura com animais não humanos sobre Epigenética, estresse e cuidados maternais. Apresenta também alguns estudos com humanos que mostram tais efeitos, destacando-se aqueles que infl uenciam ou são infl uenciados pelo comportamento operante. A partir da investigação realizada encontrou-se que cuidados maternais pós-parto são uma condição ambiental que produz efeitos no eixo hipotálamo-pituitária-adrenal (HPA), participando da composição da vulnerabilidade ao estresse. Seus possíveis efeitos fi siológicos no condicionamento operante sinalizam alternativas para intervenções baseadas na plasticidade da formação do epigenoma. Este conhecimento, além de promover a aproximação entre a Epigenética e a Análise do Comportamento em nível básico por meio de estudos com animais não humanos, poderá contribuir em nível aplicado para um melhor entendimento do neurodesenvolvimento infantil e adequado planejamento de intervenções efetivas com mães e fi lhos. Palavras-chave: Cuidados maternais, Epigenética, vulnerabilidade ao estresse, neurodesenvolvimento, Análise do Comportamento. AbstractMaternal care is an early life experience that has been consistently related to alterations in the genetic expression through epigenetic mechanisms such as DNA methylation or DNA histone modifi cation. The present study aims to present a theoretical investigation about maternal care as an environmental event that may produce epigenetic alterations related to the biological bases of stress vulnerability. The research was based on empirical studies as well as literature review on non-human animals concerning epigenetics, stress and maternal care. It also presents some studies on humans that show such effects, particularly the ones that infl uence or are infl uenced by the operant behavior. Post-natal maternal care is found to cause effects on the hypothalamic-pituitary-adrenal (HPA) axis activity participating in the building of stress vulnerability. Its possible physiological effects on the operant conditioning point out to alternatives to intervention based on the plasticity of the epigenome formation. This knowledge enhances the proximity between Epigenetics and Behavior Analysis at a basic level through studies with non-human animals and at an applied level through a better understanding of child neurodevelopment and proper planning of effective intervention with mothers and children. Keywords: Maternal care, Epigenetics, stress vulnerability, neurodevelopment, Behavior Analysis. * Endereço para correspondência: R. Prof. Samuel Moura, 367...

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Early life genetic, epigenetic and environmental factors shaping emotionality in rodents

Cited by 268 publications

References 183 publications

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Ontogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice

Epigenética, Cuidados Maternais e Vulnerabilidade ao Estresse: Conceitos Básicos e Aplicabilidade

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