通过光生物调节疗法激活AKT/GSK-3β/β-连环蛋白信号通路可促进新生大鼠缺氧缺血性脑损伤模型中神经干细胞的增殖。

Activation of the AKT/GSK-3β/β-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

作者信息

Liao Zhaoying, Zhou Xuanzi, Li Siyu, Jiang Wei, Li Tingsong, Wang Nanqing, Xiao Nong

机构信息

Department of Rehabilitation, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing, China.

出版信息

Ann Transl Med. 2022 Jan;10(2):55. doi: 10.21037/atm-21-5619.

BACKGROUND

Hypoxic-ischemic brain damage (HIBD) significantly affects neurodevelopment in infants and is a leading cause of severe neurological morbidity and mortality in neonates. Our previous study found that photobiomodulation therapy (PBMT) improves the impaired spatial learning and memory of HIBD rat models. However, the neuroprotective mechanism conferred by PBMT in HIBD is unclear.

METHODS

In the present study, HIBD model rats were treated with PBMT at 5 mW/cm per day in the dark for 14 days (10 min each day), and primary neural stem cells (NSCs) after oxygen-glucose deprivation (OGD) were treated with PBMT for 10 min at 1, 5, 10, and 20 mW/cm in the dark. PBMT promoted hippocampal neural stem cell (NSC) proliferation and .

RESULTS

Mechanistically, PBMT upregulated phosphatidylinositol 3 kinase (PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3 beta (p-GSK-3β), β-catenin, and cyclin D1 expression and , promoting NSC proliferation. Furthermore, both LY294002 (a PI3K inhibitor) and IWR-1 (a Wnt/β-catenin inhibitor) inhibited the PBMT promotion of NSC proliferation after OGD and suppressed β-catenin and cyclin D1 expression .

CONCLUSIONS

PBMT improved the spatial learning and memory of HIBD rats and promoted hippocampal NSC proliferation through the AKT/GSK-3β/β-catenin pathway.

背景

缺氧缺血性脑损伤（HIBD）显著影响婴儿的神经发育，是新生儿严重神经疾病和死亡的主要原因。我们之前的研究发现，光生物调节疗法（PBMT）可改善HIBD大鼠模型受损的空间学习和记忆能力。然而，PBMT在HIBD中的神经保护机制尚不清楚。

方法

在本研究中，HIBD模型大鼠在黑暗中每天接受5 mW/cm的PBMT治疗，持续14天（每天10分钟），氧糖剥夺（OGD）后的原代神经干细胞（NSC）在黑暗中分别接受1、5、10和20 mW/cm的PBMT治疗10分钟。PBMT促进海马神经干细胞（NSC）增殖。

结果

从机制上讲，PBMT上调磷脂酰肌醇3激酶（PI3K）、磷酸化蛋白激酶B（p-AKT）、磷酸化糖原合酶激酶3β（p-GSK-3β）、β-连环蛋白和细胞周期蛋白D1的表达，促进NSC增殖。此外，LY294002（一种PI3K抑制剂）和IWR-1（一种Wnt/β-连环蛋白抑制剂）均抑制了OGD后PBMT对NSC增殖的促进作用，并抑制了β-连环蛋白和细胞周期蛋白D1的表达。