Pathological analysis of changes in intracellular energy metabolism during wallerian degeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17967
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Osaka University
• Principal Investigator: Takenaka Tomofumi 大阪大学, 医学部附属病院, 医員 (60869527)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ワーラー変性 / 解糖系 / アデノシン3リン酸 / ミトコンドリア

Outline of Final Research Achievements

Axonal injury causes Wallerian degeneration (WD) in the distal nerve stump, but adenosine triphosphate (ATP) behavior remains unclear. We examined the change in ATP levels and biochemical pathways associated with WD using the GO-ATeam2 knock-in mouse and rat sciatic nerve transection model and in vivo ATP imaging. In the distal stump after axotomy, ATP levels gradually decreased with WD progression. The glycolytic system and monocarboxylate transport via MCTs were also activated, with the progression of mitochondrial atypicality in axons. Our findings suggest that in the distal nerve stump, the glycolytic system and monocarboxylate transport via MCTs are activated to supply axonal ATP. Our study provides a basis for understanding the bioenergetics during WD, and could be used in the development of therapeutic agents.

Free Research Field

神経代謝

Academic Significance and Societal Importance of the Research Achievements

本研究は、ワーラー変性におけるエネルギー代謝（ATP）の詳細な動態に加え、今まで明らかにされていなかったエネルギー産生に関わる経路を明らかにした。ワーラー変性は、代表的である末梢神経の損傷以外にも脳卒中や変性疾患など、ほぼすべての神経系疾患において共通してみられる病態である。したがって、本研究の発展によって、これら神経系疾患に対する病態の理解が進むとともに、将来的な創薬・治療開発に寄与する可能性が期待できる。