Downregulation of microRNA-124-3p promotes subventricular zone neural stem cell activation by enhancing the function of BDNF downstream pathways after traumatic brain injury in adult rats.
Downregulation of microRNA-124-3p promotes subventricular zone neural stem cell activation by enhancing the function of BDNF downstream pathways after traumatic brain injury in adult rats.
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microRNA-124- 3 p下调通过增强成年大鼠创伤性脑损伤后BDNF下游通路的功能促进室管膜下区神经干细胞活化
DOI：
10.1111/cns.13845
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发表时间：
2022-07
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
在这项研究中，研究了脑室内注射miR-124 - 3 p agomir或apomir对中度创伤性脑损伤（TBI）成年大鼠的预后和脑室下区（SVZ）神经干细胞（NSC）的影响。如前所述建立并验证具有中度受控皮质撞击（CCI）的模型大鼠。分析SVZ中miR-124 - 3 p的动态变化和NSCs的状态。为了评估TBI后侧脑室注射miR-124 - 3 p类似物和抑制剂的效果，使用改良的神经系统严重程度评分（mNSS）和旋转杆试验评估运动功能预后。还探索了SVZ NSC标志物表达的变化。对预测的miR-124 - 3 p靶点进行京都基因和基因组百科全书（KEGG）途径富集分析，以推断miR-124 - 3 p功能，并进一步探索miR-124 - 3 p对关键预测靶点的影响。miR-124抑制剂的施用增强了SVZ NSC增殖并改善了TBI大鼠的运动功能。对miR-124靶点的功能分析揭示了miR-124与神经营养因子信号通路之间的高度相关性，尤其是TrkB下游通路。PI 3 K、Akt 3和Ras被发现是关键的miR-124靶点，并参与大多数预测的功能途径。干扰侧脑室中的miR-124表达会影响SVZ中的PI 3 K/Akt 3和Ras通路，并且miR-124抑制剂增强了脑源性神经营养因子（BDNF）在TBI后SVZ NSC增殖中的效力。通过侧脑室注射破坏miR-124表达对神经再生和TBI预后具有有益影响。此外，联合使用BDNF和miR-124抑制剂可能比单独使用BDNF治疗TBI的结果更好。miR-124抑制剂的施用增强了TBI大鼠中SVZ NSC的活化。这一过程部分是通过上调BDNF下游的PI 3 K/Akt 3和Ras信号通路来实现的。
In this study, the effect of intracerebral ventricle injection with a miR‐124‐3p agomir or antagomir on prognosis and on subventricular zone (SVZ) neural stem cells (NSCs) in adult rats with moderate traumatic brain injury (TBI) was investigated. Model rats with moderate controlled cortical impact (CCI) were established and verified as described previously. The dynamic changes in miR‐124‐3p and the status of NSCs in the SVZ were analyzed. To evaluate the effect of lateral ventricle injection with miR‐124‐3p analogs and inhibitors after TBI, modified neurological severity scores (mNSSs) and rotarod tests were used to assess motor function prognosis. The variation in SVZ NSC marker expression was also explored. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of predicted miR‐124‐3p targets was performed to infer miR‐124‐3p functions, and miR‐124‐3p effects on pivotal predicted targets were further explored. Administration of miR‐124 inhibitors enhanced SVZ NSC proliferation and improved the motor function of TBI rats. Functional analysis of miR‐124 targets revealed high correlations between miR‐124 and neurotrophin signaling pathways, especially the TrkB downstream pathway. PI3K, Akt3, and Ras were found to be crucial miR‐124 targets and to be involved in most predicted functional pathways. Interference with miR‐124 expression in the lateral ventricle affected the PI3K/Akt3 and Ras pathways in the SVZ, and miR‐124 inhibitors intensified the potency of brain‐derived neurotrophic factor (BDNF) in SVZ NSC proliferation after TBI. Disrupting miR‐124 expression through lateral ventricle injection has beneficial effects on neuroregeneration and TBI prognosis. Moreover, the combined use of BDNF and miR‐124 inhibitors might lead to better outcomes in TBI than BDNF treatment alone. Administration of miR‐124 inhibitors enhances SVZ NSCs activation in TBI rats. Such process is partly achieved by up‐regulating BDNF downstream PI3K/Akt3 and Ras signaling pathways.
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影响因子：
4.2
作者：
HAMM, RJ;PIKE, BR;JENKINS, LW
通讯作者：
JENKINS, LW
影响因子：
4
作者：
Kowiański P;Lietzau G;Czuba E;Waśkow M;Steliga A;Moryś J
通讯作者：
Moryś J
影响因子：
16.6
作者：
Marqués-Torrejón MÁ;Williams CAC;Southgate B;Alfazema N;Clements MP;Garcia-Diaz C;Blin C;Arranz-Emparan N;Fraser J;Gammoh N;Parrinello S;Pollard SM
通讯作者：
Pollard SM
DOI：
10.1177/0271678x21999553
发表时间：
2021-09
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Chandra PK;Cikic S;Baddoo MC;Rutkai I;Guidry JJ;Flemington EK;Katakam PV;Busija DW
通讯作者：
Busija DW
影响因子：
4.6
作者：
Elton TS;Yalowich JC
通讯作者：
Yalowich JC