关键词: DREADD calcium imaging cell therapy chemogenetics functional connectivity indicator monosynaptic tracing optogenetics rabies virus sensor

来  源:   DOI:10.3390/bioengineering11050487   PDF(Pubmed)

Abstract:
Cell therapy has proven to be a promising treatment for a range of neurological disorders, including Parkinson Disease, drug-resistant epilepsy, and stroke, by restoring function after brain damage. Nevertheless, evaluating the true effectiveness of these therapeutic interventions requires a deep understanding of the functional integration of grafted cells into existing neural networks. This review explores a powerful arsenal of molecular techniques revolutionizing our ability to unveil functional integration of grafted cells within the host brain. From precise manipulation of neuronal activity to pinpoint the functional contribution of transplanted cells by using opto- and chemo-genetics, to real-time monitoring of neuronal dynamics shedding light on functional connectivity within the reconstructed circuits by using genetically encoded (calcium) indicators in vivo. Finally, structural reconstruction and mapping communication pathways between grafted and host neurons can be achieved by monosynaptic tracing with viral vectors. The cutting-edge toolbox presented here holds immense promise for elucidating the impact of cell therapy on neural circuitry and guiding the development of more effective treatments for neurological disorders.
摘要:
细胞疗法已被证明是一系列神经系统疾病的有希望的治疗方法,包括帕金森病,耐药癫痫,和中风,通过恢复脑损伤后的功能。然而,评估这些治疗干预措施的真正有效性需要深入了解移植细胞与现有神经网络的功能整合.这篇综述探讨了强大的分子技术库,彻底改变了我们揭示移植细胞在宿主大脑中功能整合的能力。通过使用光遗传学和化学遗传学,从精确操纵神经元活动到查明移植细胞的功能贡献,通过在体内使用基因编码(钙)指标来实时监测神经元动力学,从而揭示重建回路内的功能连通性。最后,移植神经元和宿主神经元之间的结构重建和映射通信途径可以通过病毒载体的单突触追踪来实现。这里介绍的尖端工具箱对于阐明细胞疗法对神经回路的影响并指导开发更有效的神经系统疾病治疗方法具有巨大的希望。
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