Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Department of Intensive Care Unit of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Neurochem Res. 2023 Aug;48(8):2406-2423. doi: 10.1007/s11064-023-03909-9. Epub 2023 Mar 28.
The available data on the localization of transforming growth factor beta1 (TGF-β1), glial cell line-derived neurotrophic factor (GDNF), and platelet-derived growth factor-BB (PDGF-BB) in the adult primate and human central nervous system (CNS) are limited and lack comprehensive and systematic information. This study aimed to investigate the cellular localization and distribution of TGF-β1, GDNF, and PDGF-BB in the CNS of adult rhesus macaque (Macaca mulatta). Seven adult rhesus macaques were included in the study. The protein levels of TGF-β1, PDGF-BB, and GDNF in the cerebral cortex, cerebellum, hippocampus, and spinal cord were analyzed by western blotting. The expression and location of TGF-β1, PDGF-BB, and GDNF in the brain and spinal cord was examined by immunohistochemistry and immunofluorescence staining, respectively. The mRNA expression of TGF-β1, PDGF-BB, and GDNF was detected by in situ hybridization. The molecular weight of TGF-β1, PDGF-BB, and GDNF in the homogenate of spinal cord was 25 KDa, 30 KDa, and 34 KDa, respectively. Immunolabeling revealed GDNF was ubiquitously distributed in the cerebral cortex, hippocampal formation, basal nuclei, thalamus, hypothalamus, brainstem, cerebellum, and spinal cord. TGF-β1 was least distributed and found only in the medulla oblongata and spinal cord, and PDGF-BB expression was also limited and present only in the brainstem and spinal cord. Besides, TGF-β1, PDGF-BB, and GDNF were localized in the astrocytes and microglia of spinal cord and hippocampus, and their expression was mainly found in the cytoplasm and primary dendrites. The mRNA of TGF-β1, PDGF-BB, and GDNF was localized to neuronal subpopulations in the spinal cord and cerebellum. These findings suggest that TGF-β1, GDNF and PDGF-BB may be associated with neuronal survival, neural regeneration and functional recovery in the CNS of adult rhesus macaques, providing the potential insights into the development or refinement of therapies based on these factors.
转化生长因子-β1(TGF-β1)、胶质细胞源性神经营养因子(GDNF)和血小板衍生生长因子-BB(PDGF-BB)在成年灵长类和人类中枢神经系统(CNS)中的定位数据有限,缺乏全面系统的信息。本研究旨在探讨 TGF-β1、GDNF 和 PDGF-BB 在成年恒河猴(Macaca mulatta)中枢神经系统中的细胞定位和分布。纳入 7 只成年恒河猴进行研究。采用 Western blot 法检测大脑皮质、小脑、海马和脊髓中 TGF-β1、PDGF-BB 和 GDNF 的蛋白水平。采用免疫组化和免疫荧光染色分别检测大脑和脊髓中 TGF-β1、PDGF-BB 和 GDNF 的表达和定位。采用原位杂交检测 TGF-β1、PDGF-BB 和 GDNF 的 mRNA 表达。脊髓匀浆中 TGF-β1、PDGF-BB 和 GDNF 的分子量分别为 25 kDa、30 kDa 和 34 kDa。免疫标记显示 GDNF 广泛分布于大脑皮质、海马结构、基底核、丘脑、下丘脑、脑干、小脑和脊髓。TGF-β1 分布最少,仅见于延髓和脊髓,PDGF-BB 表达也有限,仅见于脑干和脊髓。此外,TGF-β1、PDGF-BB 和 GDNF 定位于脊髓和海马的星形胶质细胞和小胶质细胞,其表达主要位于细胞质和初级树突。TGF-β1、PDGF-BB 和 GDNF 的 mRNA 定位于脊髓和小脑的神经元亚群。这些发现表明,TGF-β1、GDNF 和 PDGF-BB 可能与成年恒河猴中枢神经系统中的神经元存活、神经再生和功能恢复有关,为基于这些因子的治疗方法的发展或完善提供了潜在的思路。