Faculty of Psychology, International Telematic University Uninettuno, Rome, Italy; Center for Behavioral Sciences and Mental Health, IstitutoSuperiore di Sanità, Rome, Italy.
Faculty of Psychology, International Telematic University Uninettuno, Rome, Italy.
Neurosci Lett. 2023 Jul 27;810:137352. doi: 10.1016/j.neulet.2023.137352. Epub 2023 Jun 14.
Dopamine plays important roles in implicit memory and motivation of behavior. Environmental inputs can produce transgenerational epigenetic changes. This concept also includes the uterus: experimentally, we sought to create hyper-dopaminergic uterine conditions through ineffective dopamine-transporter (DAT) protein, obtained by inserting a stop-codon into the SLC6A3 gene. By crossing WT-dam with KO-sire (or vice-versa), we obtained a 100% DAT-heterozygous (HET) offspring with known derivation of the wild allele: MAT rats are offspring of WT-female and KO-male; PAT rats are offspring of KO-female and WT-male. We reconstructed inheritance of alleles, by crossing PAT-male with MAT-female or vice-versa, obtaining GIX (PAT-male with MAT-female) and DIX (MAT-male with PAT-female) rats (such offspring present specular paths in allele inheritance from grandparents). We conducted three experiments: first, we assessed maternal behaviour (four epigenotypes: WT, MAT, PAT and WHZ=HET-pups fostered-to-a WT-dam); in the second, we analysed sleep-wake cycles of GIX and DIX epigenotypes with their WIT siblings as controls; in the third, we explored the impact of WT or MAT mother on WT or HET pups. MAT-dams (with GIX-pups) express excessive licking/grooming. However, in the mere presence of "sick" epigenotype, PAT-dams (with DIX-pups) and also WHZ (i.e., WT-dams but with HET-pups) expressed greater nest-building care towards the offspring, compared to "true-wild" litters (WT-dams with WT-pups). In Exp. 2 at adolescence, GIX epigenotype showed locomotor hyperactivity during late waking-phase, while DIX epigenotype exhibited pronounced hypoactivity compared to controls. In Exp. 3, we confirmed that HET adolescent pups receiving cares from a MAT-dam may develop additional hyperactivity when awake, but additional hypoactivity during rest-hours. Thus, behavioral changes observed in DAT-heterozygous offspring have opposite courses based on of DAT-allele inheritance from a grandparent through the sire or the dam. In conclusion, behavioural changes in the offspring have antithetic courses with respect to inheritance of DAT-allele via sperm or egg.
多巴胺在隐性记忆和行为动机中发挥着重要作用。环境输入可以产生跨代表观遗传变化。这个概念也包括子宫：通过实验，我们试图通过插入一个终止密码子到 SLC6A3 基因中来创建超多巴胺能的子宫条件。通过将 WT-母鼠与 KO-父鼠（或反之亦然）杂交，我们得到了 100%的多巴胺转运蛋白（DAT）杂合子（HET）后代，其野生等位基因的来源已知：MAT 大鼠是 WT-母鼠和 KO-公鼠的后代；PAT 大鼠是 KO-母鼠和 WT-公鼠的后代。我们通过将 PAT-公鼠与 MAT-母鼠或反之杂交，重建了等位基因的遗传，得到了 GIX（PAT-公鼠与 MAT-母鼠）和 DIX（MAT-公鼠与 PAT-母鼠）大鼠（这些后代的等位基因遗传途径从祖父母那里是镜像的）。我们进行了三项实验：首先，我们评估了母性行为（四个表型：WT、MAT、PAT 和 WHZ=HET-幼崽寄养给 WT-母鼠）；其次，我们分析了 GIX 和 DIX 表型与其 WIT 同窝仔的睡眠-觉醒周期作为对照；最后，我们探索了 WT 或 MAT 母亲对 WT 或 HET 幼崽的影响。MAT-母鼠（有 GIX-幼崽）表现出过度的舔舐/梳理行为。然而，在仅仅存在“病态”表型的情况下，PAT-母鼠（有 DIX-幼崽）和 WHZ（即 WT-母鼠但有 HET-幼崽）对后代表现出更大的筑巢护理，与“真正野生”窝仔（WT-母鼠和 WT-幼崽）相比。在实验 2 中，青春期的 GIX 表型在晚觉醒期表现出运动过度活跃，而 DIX 表型与对照组相比表现出明显的活动减少。在实验 3 中，我们证实，HET 青春期幼崽从 MAT-母鼠那里得到照顾，可能会在清醒时出现额外的过度活跃，但在休息时间会出现额外的活动减少。因此，在 DAT 杂合子后代中观察到的行为变化基于从祖父辈通过父本或母本遗传的 DAT 等位基因而呈现相反的过程。总之，在 DAT 等位基因通过精子或卵子遗传的情况下，后代的行为变化具有对偶性。
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