Oestrogen treatment restores dentate gyrus development in premature newborns by IGF1 regulation.
Oestrogen treatment restores dentate gyrus development in premature newborns by IGF1 regulation.
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DOI：
10.1111/jcmm.17816
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发表时间：
2023-09
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
在新生儿病房照顾的早产儿患有记忆和学习缺陷。早产减少海马齿状回（DG）的神经发生和突触发生。这种神经元的不成熟归因于PSD95、NMDR2A和IGF1水平的升高。由于雌激素治疗在DG的发育和可塑性中起着关键作用，我们假设17β‐雌二醇（E2）治疗可以改善DG的神经发生和突触发生，逆转早产新生儿的认知缺陷。此外，E2诱导的恢复可能由IGF1信号介导。这些假设在兔的早产和非母性护理模型中得到了检验，在该模型中，由实验室人员灌食和饲养早产儿。我们比较了E2和载体处理的早产儿试剂盒的形态、分子和行为参数。我们还用雌激素降解剂RAD1901处理试剂盒，并评估IGF1信号传导。我们发现E2处理增加了DG中Tbr2+和DCX+神经元祖细胞的数量，增加了谷氨酸突触的密度。E2治疗可恢复早产儿PSD95和NMDAR2A水平及认知功能。转录组学分析表明，E2治疗通过影响IGF1R与神经退行性和谷氨酸能基因之间的相互作用有助于恢复。E2治疗结束后，ERα表达在D7降低，随后D30升高。E2诱导的ERα水平波动与D7时IGF1/2表达升高和D30时表达降低相关。RAD1901处理的ERα降解提高了IGF1水平，表明ERα抑制IGF1的表达。E2治疗可通过调节ERα和IGF1水平减轻早产诱导的DG发育不良和认知功能障碍。
Prematurely‐born infants cared for in the neonatal units suffer from memory and learning deficits. Prematurity diminishes neurogenesis and synaptogenesis in the hippocampal dentate gyrus (DG). This dysmaturation of neurons is attributed to elevated PSD95, NMDR2A, and IGF1 levels. Since oestrogen treatment plays key roles in the development and plasticity of DG, we hypothesized that 17β‐estradiol (E2) treatment would ameliorate neurogenesis and synaptogenesis in the DG, reversing cognitive deficits in premature newborns. Additionally, E2‐induced recovery would be mediated by IGF1 signalling. These hypotheses were tested in a rabbit model of prematurity and nonmaternal care, in which premature kits were gavage‐fed and reared by laboratory personnel. We compared E2‐ and vehicle‐treated preterm kits for morphological, molecular, and behavioural parameters. We also treated kits with oestrogen degrader, RAD1901, and assessed IGF1 signalling. We found that E2 treatment increased the number of Tbr2+ and DCX+ neuronal progenitors and increased the density of glutamatergic synapses in the DG. E2 treatment restored PSD95 and NMDAR2A levels and cognitive function in preterm kits. Transcriptomic analyses showed that E2 treatment contributed to recovery by influencing interactions between IGF1R and neurodegenerative, as well as glutamatergic genes. ERα expression was reduced on completion of E2 treatment at D7, followed by D30 elevation. E2‐induced fluctuation in ERα levels was associated with a reciprocal elevation in IGF1/2 expression at D7 and reduction at D30. ERα degradation by RAD1901 treatment enhanced IGF1 levels, suggesting ERα inhibits IGF1 expression. E2 treatment alleviates the prematurity‐induced maldevelopment of DG and cognitive dysfunctions by regulating ERα and IGF1 levels.
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影响因子：
4.2
作者：
Gerstner, Bettina;Lee, Joan;DeSilva, Tara M.;Jensen, Frances E.;Volpe, Joseph J.;Rosenberg, Paul A.
通讯作者：
Rosenberg, Paul A.
影响因子：
3.4
作者：
Hilton, Genell D.;Nunez, Joseph L.;McCarthy, Margaret M.
通讯作者：
McCarthy, Margaret M.
DOI：
10.1111/j.1469-8749.2011.04150.x
发表时间：
2012-03-01
影响因子：
3.8
作者：
Aarnoudse-Moens, Cornelieke S. H.;Duivenvoorden, Hugo J.;Oosterlaan, Jaap
通讯作者：
Oosterlaan, Jaap
影响因子：
5.3
作者：
Grove, M;Demyanenko, G;Pendergast, AM
通讯作者：
Pendergast, AM
影响因子：
4.8
作者：
Hedderich DM;Avram M;Menegaux A;Nuttall R;Zimmermann J;Schneider SC;Schmitz-Koep B;Daamen M;Scheef L;Boecker H;Zimmer C;Baumann N;Bartmann P;Wolke D;Bäuml JG;Sorg C
通讯作者：
Sorg C