Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration
作者机构：Laboratory of Developmental Biology Department of Biology University of Patras Laboratory of Cellular and Molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras
出 版 物：《Neural Regeneration Research》 (中国神经再生研究(英文版))
年 卷 期：2024年第19卷第6期
页 面：1318-1324页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学]
基 金：co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme《Human Resources Development Education and Lifelong Learning 2014–2020》in the context of the project “NeuroProPar”(MIS 5047138 to IK)
主 题：adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson’s disease substantia
摘 要：We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.
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