美国弗里德曼大脑研究所Ian Maze团队揭示多巴胺驱动母体大脑的持续重塑。2026年5月20日出版的《自然》杂志发表了这项成果。

在这里，该课题组以全脑转录组学分析为主题来定义生殖经验诱导的神经可塑性的分子景观，并确定海马背侧形成（dHF）是转录重塑的关键位点。结合单细胞RNA测序和母崽分离模式，课题组研究人员还发现慢性产后应激通过改变多巴胺动力学显著破坏dHF适应，导致多巴胺依赖组蛋白翻译后修饰H3多巴胺化的变化，而H3多巴胺化会间接介导下游基因表达和行为的改变。

在人类背下带（dHF内的一个大脑结构）中，该课题组发现了H3多巴胺化和转录中偶对依赖性改变的保守模式。该研究团队进一步通过化学遗传学抑制多巴胺释放到dHF，确立了多巴胺调节在调节这些适应性中的充分性，这概括了处女雌性小鼠生殖经验的关键表观基因组和行为特征。总之，他们的研究结果证实了多巴胺是人类和小鼠的奇偶诱导神经适应的中心调节器，揭示了一种基本的转录机制，通过这种机制，女性的生殖经历重塑了大脑，以维持长期的行为适应。

据了解，怀孕和产后经历代表了对母亲身体和大脑施加持久需求的变革性生理状态，导致终身神经适应。然而，驱动这些持续变化的精确分子机制仍然知之甚少。

附：英文原文

Title: Dopamine drives persistent remodelling of the maternal brain

Author: OChan, Jennifer C., Di Salvo, Giuseppina, Cunningham, Ashley M., Dutta, Sohini, Brindley, Elizabeth, Weekley, Benjamin H., Chen, Winnie, Iyer, Rasika R., Wan, Ethan, Zhang, Cindy, Mechawar, Naguib, Turecki, Gustavo, Maze, Ian

Issue&Volume: 2026-05-20

Abstract: Pregnancy and postpartum experiences represent transformative physiological states that impose lasting demands on the maternal body and brain, resulting in lifelong neural adaptations1,2,3,4,5,6. However, the precise molecular mechanisms that drive these persistent alterations remain poorly understood. Here we used brain-wide transcriptomic profiling to define the molecular landscape of neuroplasticity induced by reproductive experience, identifying the dorsal hippocampal formation (dHF) as a key site of transcriptional remodelling. Combining single-cell RNA sequencing with a maternal–pup separation paradigm, we additionally found that chronic postpartum stress significantly disrupts dHF adaptations by altering dopamine dynamics, leading to changes in the dopamine-dependent histone post-translational modification, H3 dopaminylation, which causally mediates downstream alterations in gene expression and behaviour. In human dorsal subiculum, a brain structure within the dHF, we uncovered conserved patterns of parity-dependent alterations in H3 dopaminylation and transcription. We further established the sufficiency of dopamine modulation in regulating these adaptations via chemogenetic suppression of dopamine release into the dHF, which recapitulated key epigenomic and behavioural features of reproductive experience in virgin female mice. In sum, our findings establish dopamine as a central regulator of parity-induced neuroadaptations in humans and mice, revealing a fundamental transcriptional mechanism by which female reproductive experience remodels the brain to sustain long-term behavioural adaptations.

DOI: 10.1038/s41586-026-10509-4

Source: https://www.nature.com/articles/s41586-026-10509-4