Neuronal RBM5 modulates cell signaling responses to traumatic and hypoxic-ischemic injury in a sex-dependent manner.
Neuronal RBM5 modulates cell signaling responses to traumatic and hypoxic-ischemic injury in a sex-dependent manner.
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DOI：
10.1038/s41420-023-01677-7
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发表时间：
2023-10-17
影响因子：
7
通讯作者：
Jackson, Travis C.
中科院分区：
文献类型：
--
作者：
Snyder, Kara;Gorse, Kiersten;Kochanek, Patrick M.;Jackson, Travis C.
目前尚不清楚抑制促死亡基因RNA结合基序5（RBM 5）是否在分离的原代神经元中具有神经保护作用，或者它是否以性别依赖的方式调节细胞存活。在这里，我们建立了性别二分法原代皮层神经元培养转基因小鼠窝藏一个floxed RBM 5基因陷阱。慢病毒介导的CRE表达用于沉默RBM 5表达。将雄性和雌性神经元维持在下一代Neurobasal-Plus培养基中，并进行机械拉伸损伤（以模拟创伤性脑损伤）或氧-葡萄糖剥夺/OGD（以模拟缺血）。RBM 5 KO不影响24小时损伤后的生存所确定的乳酸脱氢酶（LDH）的释放，在任一范例。相反，雌性KO神经元在损伤后具有增加的血影蛋白分解产物（在两种模型中）。此外，在OGD中，雄性神经元中的RBM 5 KO加剧了损伤诱导的促存活AKT激活（pAKT 473）的下调，但相反地导致雌性神经元中的pAKT 473保留。此外，全球蛋白质组学鉴定了19个差异表达（DE）蛋白在OGD损伤的男性神经元，和102 DE蛋白在损伤的女性神经元。在损伤的雄性KO神经元中鉴定了两种新的RBM 5调节蛋白（PIGQ和EST 1C），并且在损伤的雌性KO神经元中鉴定了8种新的蛋白（S35 A5、DHTK 1、STX 3、IF 3 M、RN 167、K1 C14、DYHS和MED 13）。总之，RBM 5抑制不会改变2个临床相关的兴奋性毒性损伤模型中原代小鼠神经元的神经元存活，但RBM 5确实以性别依赖性方式调节细胞内对损伤的反应。
It is not clear if inhibiting the pro-death gene RNA binding motif 5 (RBM5) is neuroprotective in isolated primary neurons or if it regulates cell survival in a sex-dependent manner. Here we established sex-dichotomized primary cortical neuron cultures from transgenic mice harboring a floxed RBM5 gene-trap. Lentivirus-mediated expression of CRE was used to silence RBM5 expression. Male and female neurons were maintained in next-generation Neurobasal-Plus media and subjected to a mechanical stretch-injury (to model traumatic brain injury) or oxygen-glucose deprivation/OGD (to model ischemia). RBM5 KO did not affect 24 h post-injury survival as determined by lactate dehydrogenase (LDH) release, in either paradigm. In contrast, female KO neurons had increased spectrin breakdown products post-insult (in both models). Furthermore, in OGD, RBM5 KO in male neurons exacerbated injury-induced downregulation of pro-survival AKT activation (pAKT473) but conversely led to pAKT473 sparing in female neurons. Moreover, global proteomics identified 19 differentially expressed (DE) proteins in OGD-injured male neurons, and 102 DE proteins in injured female neurons. Two novel RBM5-regulated proteins (PIGQ and EST1C) were identified in injured male KO neurons, and 8 novel proteins identified in injured female KO neurons (S35A5, DHTK1, STX3, IF3M, RN167, K1C14, DYHS, and MED13). In summary, RBM5 inhibition does not modify neuronal survival in primary mouse neurons in 2 clinically relevant models of excitotoxic insult, but RBM5 does regulate intracellular responses to injury in a sex-dependent manner.
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影响因子：
3.3
作者：
Jackson TC;Janesko-Feldman K;Gorse K;Vagni VA;Jackson EK;Kochanek PM
通讯作者：
Kochanek PM
Akt 和 mTOR 介导神经元程序性坏死
影响因子：
9
作者：
通讯作者：
--
影响因子：
5.3
作者：
Snijders Blok L;Hiatt SM;Bowling KM;Prokop JW;Engel KL;Cochran JN;Bebin EM;Bijlsma EK;Ruivenkamp CAL;Terhal P;Simon MEH;Smith R;Hurst JA;DDD study;McLaughlin H;Person R;Crunk A;Wangler MF;Streff H;Symonds JD;Zuberi SM;Elliott KS;Sanders VR;Masunga A;Hopkin RJ;Dubbs HA;Ortiz-Gonzalez XR;Pfundt R;Brunner HG;Fisher SE;Kleefstra T;Cooper GM
通讯作者：
Cooper GM
影响因子：
4.2
作者：
Farooq, Jeffrey;Snyder, Kara;Jackson, Travis C.
通讯作者：
Jackson, Travis C.
影响因子：
4.1
作者：
Hernandez-Fonseca, Karla;Massieu, Lourdes;Camacho-Arroyo, Ignacio
通讯作者：
Camacho-Arroyo, Ignacio