Transgenerational rescue of a genetic defect in long-term potentiation and memory formation by juvenile enrichment.
Transgenerational rescue of a genetic defect in long-term potentiation and memory formation by juvenile enrichment.
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DOI：
10.1523/jneurosci.5057-08.2009
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发表时间：
2009-02-04
期刊：
影响因子：
--
通讯作者：
Feig LA
中科院分区：
文献类型：
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作者：
Arai JA;Li S;Hartley DM;Feig LA
从经验中获得的品质可以遗传给后代的观点长期以来被认为与当前对遗传学的理解不相容。然而，最近关于非孟德尔式跨代遗传的文献使得这种“拉马克式”的现象更加可信。在这里，我们证明了15 d大的小鼠暴露于2周的富集环境（EE），包括暴露于新物体，增加社会互动和自愿运动，不仅在这些富集的小鼠中，而且在它们未来的后代在青春期早期也增强了长期增强（LTP），即使后代从未经历过EE。在这两代中，LTP诱导都被新出现的cAMP/p38 MAP激酶依赖性信号级联增强。引人注目的是，通常与ras-grf敲除小鼠相关的LTP缺陷和情境恐惧条件反射记忆在富集突变父母的后代中都被掩盖了。这种效应的跨代传递发生在胚胎发生期间，从富集的母亲到她的后代。如果类似的现象发生在人类身上，一个人在青春期记忆的有效性，特别是那些控制记忆的细胞信号机制有缺陷的人，可能会受到母亲在年轻时经历的环境刺激的影响。
The idea that qualities acquired from experience can be transmitted to future offspring has long been considered incompatible with current understanding of genetics. However, the recent documentation of non-Mendelian transgenerational inheritance makes such a “Lamarckian”-like phenomenon more plausible. Here, we demonstrate that exposure of 15-d-old mice to 2 weeks of an enriched environment (EE), that includes exposure to novel objects, elevated social interactions and voluntary exercise, enhances long-term potentiation (LTP) not only in these enriched mice but also in their future offspring through early adolescence, even if the offspring never experience EE. In both generations, LTP induction is augmented by a newly appearing cAMP/p38 MAP kinase-dependent signaling cascade. Strikingly, defective LTP and contextual fear conditioning memory normally associated with ras-grf knock-out mice are both masked in the offspring of enriched mutant parents. The transgenerational transmission of this effect occurs from the enriched mother to her offspring during embryogenesis. If a similar phenomenon occurs in humans, the effectiveness of one's memory during adolescence, particularly in those with defective cell signaling mechanisms that control memory, can be influenced by environmental stimulation experienced by one's mother during her youth.