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与在双亲养育结构中饲养的小鼠相比,由单亲母亲饲养的C57BL/6J后代小鼠表现出独特的神经激活模式和乙醇诱导的焦虑缓解增强。

C57BL/6J offspring mice reared by a single-mother exhibit, compared to mice reared in a biparental parenting structure, distinct neural activation patterns and heightened ethanol-induced anxiolysis.

作者信息

Pasquetta Lucila, Ferreyra Eliana, Wille-Bille Aranza, Pautassi Ricardo Marcos, Ramirez Abraham, Piovano Jesica, Molina Juan Carlos, Miranda-Morales Roberto Sebastián

机构信息

Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-Universidad Nacional de Córdoba), Friuli 2434, Córdoba, 5016, Argentina.

Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina.

出版信息

Psychopharmacology (Berl). 2025 May;242(5):1123-1135. doi: 10.1007/s00213-024-06627-4. Epub 2024 May 30.

Abstract

RATIONALE

Parenting experiences with caregivers play a key role in neurodevelopment. We recently reported that adolescents reared by a single-mother (SM) display an anxiety-prone phenotype and drink more alcohol, compared to peers derived from a biparental (BP) rearing condition.

OBJECTIVES

To investigate if SM and BP offspring infant mice exhibit differential sensitivity to ethanol-induced locomotor activity and differential activity patterns in brain areas related to anxiety response. We also analyzed anxiety response and ethanol-induced anxiolysis in SM and BP adolescents.

METHODS

Mice reared in SM or BP conditions were assessed for (a) ethanol-induced locomotor activity at infancy, (b) central expression of Fos-like proteins (likely represented mostly by FosB, a transcription factor that accumulates after chronic stimuli exposure and serves as a molecular marker of neural plasticity) and cathecolaminergic activity, and (c) anxiety-like behavior and ethanol-induced anxiolysis in adolescence.

RESULTS

Infant mice were sensitive to the stimulating effects of 2.0 g/kg alcohol, regardless parenting structure. SM mice exhibited, relative to BP mice, a significantly greater number of Fos-like positive cells in the central amygdala and basolateral amygdala nuclei. Ethanol treatment, but not parenting condition, induced greater activation of dopaminergic neurons in ventral tegmental area. SM, but not BP, adolescent mice were sensitive to ethanol-induced anxiolysis.

CONCLUSIONS

These results highlight the complex relationship between parenting experiences and neurodevelopment. The SM parenting may result in greater neural activation patterns in brain areas associated with anxiety response, potentially contributing to increased basal anxiety and alcohol sensitivity.

摘要

理论依据

与照顾者的养育经历在神经发育中起关键作用。我们最近报告称,与双亲养育环境下的同龄人相比,由单身母亲抚养长大的青少年表现出易焦虑的表型且饮酒更多。

目的

研究单身母亲和双亲养育的子代幼鼠对乙醇诱导的运动活动是否表现出不同的敏感性,以及在与焦虑反应相关的脑区是否有不同的活动模式。我们还分析了单身母亲和双亲养育的青少年的焦虑反应以及乙醇诱导的抗焦虑作用。

方法

对在单身母亲或双亲养育条件下饲养的小鼠进行以下评估:(a) 幼年期乙醇诱导的运动活动;(b) Fos样蛋白的中枢表达(可能主要由FosB代表,FosB是一种转录因子,在长期刺激暴露后积累,作为神经可塑性的分子标志物)和儿茶酚胺能活性;(c) 青春期的焦虑样行为和乙醇诱导的抗焦虑作用。

结果

无论养育结构如何,幼鼠对2.0 g/kg酒精的刺激作用均敏感。与双亲养育的小鼠相比,单身母亲养育的小鼠在中央杏仁核和基底外侧杏仁核核中Fos样阳性细胞数量显著更多。乙醇处理而非养育条件诱导腹侧被盖区多巴胺能神经元的更大激活。青春期单身母亲养育而非双亲养育的小鼠对乙醇诱导的抗焦虑作用敏感。

结论

这些结果突出了养育经历与神经发育之间的复杂关系。单身母亲养育可能导致与焦虑反应相关脑区更大的神经激活模式,可能导致基础焦虑增加和酒精敏感性增加。

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