Collaborative interdisciplinary project: exploring CNS myelin structure and myelination through imaging systems

Abstract:

Myelin sheaths, produced by oligodendrocytes, play a crucial role in the central nervous system (CNS) through insulating axons with multiple lipid-enriched layers. Myelination accelerates electrical signal propagation, not only essential for neural communications but vital for various neurological and cognitive functions, such as learning, memory, and mood regulation. Myelination also has a high plasticity in the CNS in childhood and adolescence, facilitating the connectivity of the brain circuitry. Even in adults, activity-dependent myelination can improve long-term potentiation of neurons thereby improving the performance in many aspects, including associative learning, non-associative learning, and working memory. Accordingly, neuronal wiring in the CNS is akin to a computer chip, and abnormalities or deficiencies in myelination can lead to neural dysfunction, resembling a short circuit in a poorly insulated chip. For example, conditions like multiple sclerosis, an autoimmune disease-causing demyelination, not only lead to motor disabilities but also memory problems and mood swings in affected individuals. Recently, many mood disorders are reportedly associated with improper myelination. Thus, understanding the intricate relationship between neurons and oligodendrocytes in myelination is the current trend in exploring novel approaches to uphold brain health.
 

Our objective is to advance the resolution of myelin imaging both in laboratory settings and in living organisms. We will establish a neuron-oligodendrocyte coculture platform integrated with a microfluidic device to explore myelination dynamics under optogenetic stimulation. Cutting-edge imaging methodologies will be utilized for high-resolution visualization of myelin structure, alongside real-time imaging systems to monitor the progression of myelination. Moreover, our research will include in vivo studies utilizing animal models with white matter demyelination within the brain and spinal cord. The ultimate aim is to devise efficacious therapeutic approaches aimed at protect myelin integrity against CNS disorders or fostering the process of remyelination.

Team members:

Distinguished Professor Shu-Fen Tzeng / Department of Life Sciences, National Cheng Kung University

Professor Chou-Ching Lin / Department of Neurology, National Cheng Kung University

Professor Wen-Tai Chiu / Department of Biomedical Engineering, National Cheng Kung University

Assistant Professor Chih-Yen Wang / Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University

跨領域合作計畫：透過影像系統探索中樞神經系統髓鞘結構和髓鞘形成

摘要：

髓鞘由寡突膠質細胞產生，透過具有多個富含脂質的層來絕緣軸突，在中樞神經系統(CNS)中發揮至關重要的作用。髓鞘形成加速電訊號傳播，這不僅對神經通訊至關重要，而且對各種神經和認知功能(例如學習、記憶和情緒調節)也至關重要。髓鞘形成在兒童和青少年時期的中樞神經系統中也具有很高的可塑性，有助於大腦迴路的連結。即使在成年人中，活動依賴性髓鞘形成也可以改善神經元的長期增強，進而改善許多方面的表現，包括聯想學習、非聯想學習和工作記憶。因此，中樞神經系統中的神經元接線類似於電腦晶片，髓鞘形成的異常或缺陷會導致神經功能障礙，類似於絕緣不良的晶片中的短路。例如，多發性硬化症(一種導致脫髓鞘的自體免疫疾病)不僅會導致運動障礙，還會導致受影響個體的記憶問題和情緒波動。最近，據報導許多情緒障礙與髓鞘形成不當有關。因此，了解神經元和寡突膠質細胞在髓鞘形成過程中的複雜關係是探索維護大腦健康新方法的當前趨勢。

我們的目標是提高實驗室環境和活體中髓磷脂成像的分辨率。 我們將建立一個與微流體裝置整合的神經元-寡突膠質細胞共培養平台，以探索光遺傳學刺激下的髓鞘形成動力學。將利用尖端成像方法對髓鞘結構進行高解析度可視化，並使用即時成像系統來監測髓鞘形成的進展。此外，我們的研究將包括利用大腦和脊髓內白質脫髓鞘的動物模型進行體內研究。最終目標是設計有效的治療方法，旨在保護髓磷脂完整性免受中樞神經系統疾病的影響或促進髓鞘再生過程。

團隊成員：

曾淑芬 特聘教授          國立成功大學生命科學系

林宙晴 教授                  國立成功大學神經學科

邱文泰 教授                  國立成功大學生物醫學工程學系

王之彥 助理教授          國立成功大學生物科技與產業科學系