論文 - 詳細
| RRC ID | 55779 |
|---|---|
| 著者 | Kuwamura M, Tanimura S, Hasegawa Y, Hoshiai R, Moriyama Y, Tanaka M, Takenaka S, Nagayoshi H, Izawa T, Yamate J, Kuramoto T, Serikawa T. |
| タイトル | Downregulation of aspartoacylase during the progression of myelin breakdown in the dmy mutant rat with mitochondrial magnesium channel MRS2 defect. |
| ジャーナル | Brain Res |
| Abstract |
OBJECTIVE:The dmy rat is an autosomal recessive mutant that exhibits severe rapid myelin breakdown throughout the central nervous system at 7-8 weeks of age. The dmy rat has a point mutation in Mrs2 gene, which encodes an essential component of the major electrophoretic Mg2+ influx system in the mitochondria. However, it remains unknown how mitochondrial dysfunction leads to the myelin breakdown. METHODS:We focused on the aspartoacylase (ASPA) and mitochondrion-related metabolites to clarify the mechanism of myelin pathology in dmy rats. Aspa mRNA was significantly decreased in both the gray matter and the ventral white matter of spinal cord in the dmy rats from 4 to 8 weeks of age. Very faint immunohistochemical expression for ASPA was noted in the gray and white matter of the affected dmy rats at 8 weeks. Liquid chromatography mass spectrometry revealed no different amount of N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A (CoA) in neurons, in the brain and spinal cord between the dmy and control rats. CONCLUSION:Our results indicated that the pyruvate dehydrogenase activity might be reduced due to the loss of Mg2+ transport activity in the mitochondria of the dmy rats, suggesting acetyl CoA production might be reduced. The number of oligodendrocytes was well preserved until 7 weeks. It is intriguing that prior to the myelin destruction at 7-8 weeks, disrupted expression of Aspa mRNA and ASPA protein undergoes from early stage of myelinogenesis. These data indicate that ASPA expression would be a useful index to evaluate a function of oligodendrocyte in the dmy rat. |
| 巻・号 | 1718 |
| ページ | 169-175 |
| 公開日 | 2019-9-1 |
| DOI | 10.1016/j.brainres.2019.05.017 |
| PII | S0006-8993(19)30272-0 |
| PMID | 31100216 |
| MeSH | Amidohydrolases / genetics Amidohydrolases / metabolism* Animals Brain / metabolism Cation Transport Proteins / genetics Cation Transport Proteins / metabolism* Central Nervous System / metabolism Disease Progression Female Ion Channels / metabolism Magnesium / metabolism Male Mitochondria / metabolism Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Myelin Sheath / metabolism* Neurons / metabolism Oligodendroglia / metabolism Rats Spinal Cord / metabolism |
| IF | 2.929 |
| 引用数 | 1 |
| リソース情報 | |
| ラット | WTC.DMY-Mrs2dmy/Kyo (strainID=19) TRM/Kyo (strainID=11) |