Post-mitotic neurons that re-enter the cell cycle in the brain are more likely to experience senescence, especially in Alzheimer’s disease, as revealed by a recent study. This discovery could offer valuable insights into the process of neurodegeneration, and the method used to uncover this phenomenon could be easily applied to study other specific groups of brain cells.
Post-mitotic neurons that re-enter the cell cycle in the brain are more likely to experience senescence, especially in Alzheimer’s disease, as revealed by a recent study published on April 9 in the open-access journal The PLOS Biology journal published a study by Kim Hai-Man Chow and colleagues at the Chinese University of Hong Kong. The study’s findings could help advance our understanding of the neurodegeneration process. The method used to make this discovery can also be easily applied to studying other unique populations of brain cells. Most neurons in the brain are post-mitotic, meaning they no longer divide. It was previously believed that this post-mitotic state was permanent. However, recent research has shown that a small percentage of neurons re-enter the cell cycle, but there is limited knowledge about their function.individual single nuclei and their RNA sequences, giving insight into the activities of the cells at the time of isolation. By analyzing the specific set of proteins required for each phase of the cell cycle, the authors were able to determine the phase of the cycle that each nucleus was in. The authors utilized publicly accessible databases of “snRNA-seq” data to gather this information, shedding light on the activities of over 30,000 individual nuclei.The researchers analyzed nuclei and assigned a score based on the expression of around 350 cell cycle-related genes. They discovered that a small number of excitatory neurons had re-entered the cell cycle, but did not successfully produce daughter neurons. Instead, these cells showed increased expression of genes linked to senescence, essentially waking up only to enter senescence.
Interestingly, the study also found that neurons in the brains of Alzheimer’s disease patients re-entered the cell cycle at a higher rate.The neurons that had reentered the cell cycle and aged showed greater expression of various genes linked to a higher risk of Alzheimer’s disease. This includes genes that directly contribute to the production of amyloid, the sticky protein that accumulates in the AD brain. Similarly, brains from patients with Parkinson’s disease and Lewy body dementia had a higher proportion of re-entering neurons compared to healthy brains.
The neurobiological significance of this increased re-entry in the diseased brain is still not fully understood, but the analytical approach used here may provide a deeper understanding of neuronal subpopulations within.In the brain, this research sheds light on disease mechanisms in neurodegenerative diseases.”Because of the rare existence and random localization of these cells in the brain, their molecular profiles and disease-specific heterogeneities remain unclear,” Chow said. “While experimental validations of these findings in relevant human samples will be conducted in the future, the applicability of this analytical approach in different diseases and cross-species settings offers new opportunities and insights to supplement mainstay histological-based approaches in studying the roles of these cells in brain aging and disease pathogenesis.”The researchers stated, “By using this bioinformatics analytical pipeline, the field will have a new tool to impartially analyze the re-engagement of the cell cycle and senescent neurons, and to examine their differences in healthy and diseased brains.”
