초록

[요약]파킨슨병과 같은 대뇌신경장애, 운동신경장애, 시각기능장애, 배뇨장애등의 노화 퇴행성 신경장애를 치료하고 재활하는 기술로서 광유전자 기법을 이용한 다양한 광자극 신경기능 복원 기술을 개발하였음.
신경신호 추출 시스템 개발, 이식형 초소형 다기능 신경전극 개발, 광감응 변위 쥐를 이용한 전임상 실험, 광유전자를 이용한 신경기능 회복과 이를 위한 광유전자 기술 개발이 수행되었음.
논문 28편(SCI 18편, SCIE 5편)을 게재하였으며, 특허 출원 7건, 특허 등록 8건의 정량적 성과를 얻었음.

Abstract ▼

The purpose of this study is to develop a new multi-functional optical neural stimulation technology for degenerative neural disorders, such as Parkinson’s, strokes, and Alzheimer’s, which consists of a combination of neural stem cell transplantation, optogenetic therapy, and drug delivery method.

The purpose of this study is to develop a new multi-functional optical neural stimulation technology for degenerative neural disorders, such as Parkinson’s, strokes, and Alzheimer’s, which consists of a combination of neural stem cell transplantation, optogenetic therapy, and drug delivery method.

Overall, the study consists of the following six sub-studies.
1) To derive dopaminergic neurons using optogenetics : We show that we can enhance efficiency of neural stem cell derived-dopaminergic neuronal differentiation by inducing action potential through expressing optogenetic gene. Further, after we transplant neural stem cell expressing optogenetic gene in parkinson’s disease model rat brain, among cells transplanted, a number of functional, morphological and mature dopaminergic neurons can induce behavioral recovery. So, we suggest possibility of clinical applications of optogenetic approach to stem cells.

2) To develop a neural modulation technology for brain: We developed a current control-based electrical stimulation method for nerve, a low noise amplification method for recording neural signals, and multi-channel electrical stimulators for nerve. We also developed organotopic culture conditions of brain slice, electrical and optical stimulation protocols for brain slice ex vivo, and mapped the neural circuit between subthalamic nucleus and striatum

3) To develop a multi-functional neural prosthesis: We developed all-in-one multi-functional neural prostheses, which are capable to delivering light to optogenetic target neurons, simultaneously recording electrical signals from the target neurons, and simultaneously delivering drug to the target neurons. This prothesis will be used to optically stimulate the transplanted optogenetic neurons, and to simultaneously monitor the electrophysiology of the target neurons. The drug delivery system embedded in the prosthesis is used to provide a proper biological environment necessary for transplanted neurons by delivering neurotropic factors

4) To evaluate neurophysiological efficacy and safety of optogenetic stimulation method: The neurophysiological efficacy of the optogenetic stimulation was evaluated using 6-OHDA-induced Parkinson’s animal models. The evaluation method includes tyrosine hydroxylase (TH) and Girk immunostaining methods, and PET imaging method. It also includes a variety of functional behavior tests of rodents.

5) To develop optogenetic control protocol for neurons: We developed optimal gene delivery methods for optogenetic transfection of neurons and stem cell-derived neurons. The optogenetically transfected neurons were optically stimulated with specially designed optical devices and electrophysiologically evaluated with multi-electrode array and patch clamp on the microscope. The method was first applied to test the optogenetic method for retina, and will be applied to the optogenetic brain in the second phase of the study.

6) To optimize optogenetic transfection method: To design the optimal opsins, such as ChR2 variants with improved sensitivity and stability, and the gene insertion for optimal membrane trafficking, and also the proper viral vectors, such as adeno-associated virus, for gene transfection. So far, we have developed these genes and viral vectors for retinal ON and OFF bipolar cells as well as for dental stem cell-derived neural progenitor cells.