Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons in the spinal cord and brain. Patients with ALS voluntarily control their limbs and even have difficulty breathing. Unfortunately, this disease is incurable. One of the decisions is to hide in several types of immune cells that defenders of human organisms. First, scientists focus on microglia, which are persistent residential central nervous system macrophages. These cells play a crucial role in maintaining brain and spinal homeostasis and providing phagocytosis, eliminating injured neurons or debris. Microglia functions in ALS are not direct, but complex and multifaceted, posing a major challenge to scientists’ understanding. Activated microglia are highly heterogeneous cells with many subpopulations regulated by genetic background and all other related genes that may interact with the gene of interest. However, the precise effect of the genetic background on specific forms of microglia and its interaction with other forms of immune cells in the ALS-driven pathological mechanism is unclear.
Investigation on the effect of genetic background changes on microglia heterogeneity and function in ALS mouse models was led by Dr. Okiru Komine and Professor Koji Yamanaka from the Department of Neuroscience and Pathology with their team at the university . The team includes Professor Tomoo Ogi from the Department of Genetics, RIEM, Naogya University and Associate Professor Kunihiko Hinohara from the Department of Immunology at the Graduate School of Medicine, Naogya University, and Kunihiko Hinohara from the Department of Immunology at the Graduate School of Medicine, Naogya University, who have made great progress in understanding the pathological properties of ALS. Their collective efforts underline the importance of collaboration in promoting knowledge of neurodegenerative diseases.
This pioneering article published in Iscience is the first to reveal the profound effects of genetic background variation on microglia heterogeneity in two different ALS model mice. This study, conducted with meticulous methods, such as behavioral, molecular, cell biology and genetic techniques, including single-cell RNA sequencing analysis, enables new insights on the impact of genetic diversity on ALS microglia subpopulations New insights. Detailed single-cell RNA sequencing analysis revealed microglia heterogeneity in twelve gene expression groups, thus significantly promoting our understanding of ALS pathology.
Professor Koji Yamanaka explained: “The mouse model with mutations in the gene-encoding special enzyme superoxide dismutase 1 used in the ALS study is the best choice for studying microglia heterogeneity infiltration into the spinal cord and affecting the infiltration of cells into the spinal cord and affecting the Disease-associated microglia (DAM) genes. “Our study affirms the correlation between microglia heterogeneity and systemic immune environment in mice with albinism and black ALS model. In addition, We identified elevated expression levels of neuroprotective genes, suggesting that there are a subset of genes in the black mouse model that may have the potential to confer neuroprotective effects on ALS progression. “The understanding of how motor neurons defend during ALS is the disease treatment One of the clues.
This study further announces the number of infiltrated cells and the ratio of peripheral immune cells between black and albino mouse models at the end stage of the disease. Some dam gene markers showed opposite regulation between microglia in black and albino mice. “Based on our current and previous studies, we suggest that environmental factors from peripheral immune cells and/or infiltrated immune cells may affect disease progression by regulating survival and dam induction in ALS model mice,” stressed Dr. Okiru Komine. In summary, extensive research conducted by Dr. Okiru Komine, Professor Koji Yamanaka and his highly qualified team revealed the significant impact of genetic background variation on microglia heterogeneity, its response and disease progression in ALS model mice. However, since the experiment was limited to two strains, the team emphasized the need for further analysis involving ALS model mice with different genetic backgrounds. This is crucial for a comprehensive understanding of potential treatments that pave the way for fundamental mechanisms.
Journal Reference
Okiru Komine, Syuhei Ohnuma, Kunihiko Hinohara, Yuichiro Hara, Mayuko Shimada, Tomohiro Akashi, Seiji Watanabe, Akira Sobue, Noe Kawade, Tomoo Ogi, Tomoo Ogi and Koji Yamanaka. “Genetic background variation affects microglia heterogeneity and disease progression in amyotrophic lateral sclerosis model mice.” Iscience 27 (2024) 108872.
doi: https://doi.org/10.1016/j.isci.2024.108872.
About the Author
Dr. Okiru Komine He is a lecturer in the Department of Neuroscience and Pathology, Institute of Environmental Medicine, Nagoya University, Japan. Dr. Komine received his BS and Masters degree. He was awarded the Tokyo University of Science in 2001 and 2003. He received his Ph.D. He set out from Tokyo University of Medicine and Dental in 2007. His main research areas are neuroinflammation in neuroinflammatory diseases such as amyotrophic transverse sclerosis and Alzheimer’s disease. Recently, he has also focused on the role of the immune system in these diseases. He likes to play tennis.
