The researchers found that the accumulation of cellular debris in microglia as the brain ages causes an increase in autofluorescence, making it harder for microglia to perform their garbage collection tasks and leading to cellular stress, damage, accumulation of fats and iron, altered metabolic processes, and an overactive immune response, causing neurological injury and neurodegenerative diseases.
Researchers at the Trinity Biomedical Sciences Institute (TBSI) have made a significant discovery regarding the aging process in the brain. For the first time, they have established a connection between the heightened presence of specialized immune cells and conditions such as Alzheimer’sAlzheimer's disease is a disease that attacks the brain, causing a decline in mental ability that worsens over time. It is the most common form of dementia and accounts for 60 to 80 percent of dementia cases. There is no current cure for Alzheimer's disease, but there are medications that can help ease the symptoms.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Alzheimer’s disease and traumatic brain injury. This breakthrough may lead to the development of new therapies focused on treating neurological diseases that occur as a result of aging.
The study, which was a collaboration with experts at the University of Maryland School of Medicine, has shed new light on the role of microglia in the brain and spinal cord. The findings of this research were published in the prestigious international journal Science Advances<em>Science Advances</em> is a peer-reviewed, open-access scientific journal that is published by the American Association for the Advancement of Science (AAAS). It was launched in 2015 and covers a wide range of topics in the natural sciences, including biology, chemistry, earth and environmental sciences, materials science, and physics.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Science Advances.
Microglia are a unique type of immune cell whose job it is to support nerve cells, defend against invading microbes, clear debris, and remove dying nerve cells by engulfing and eating them. Emerging research indicates that microglia can have different functional responses depending on molecular and biochemical changes occurring within these specialized cells.
In fact, various subtypes of microglia can be distinguished based on a property called autofluorescence. This is the tendency of cells to emit light of one color after they have absorbed light of another, and it occurs because specific substances inside the cells absorb light. The substances stored in specialized cellular compartments include fat molecules, cholesterol crystals, metals, and other misfolded proteins.
David Loane, Assistant Professor of Neuroscience in Trinity’s School of Biochemistry and Immunology in TBSI is the lead author of the research.
He said: “As the brain ages, these materials build up inside autofluorescent microglia, which increase their autofluorescence as a result. Unfortunately, this accumulation of cellular debris also makes it harder for the microglia to perform their essential garbage collection tasks in the brain and to prevent neurological injury and neurodegenerative disease.”
He continues, “In this study, we found – in aged animals – that these microglia adopt a unique, dysfunctional state, which has a number of problematic impacts. For example, there is an increase in cellular stress and damage, an accumulation of fats and iron, alterations to metabolic processes, and an increase in production of molecules that over-egg the immune response.”
In addition, the scientists demonstrated that autofluorescent microglia and associated inflammation were more pronounced under pathological conditions, such as in genetic risk factor models of Alzheimer’s disease, and – promisingly – were reversed by drug-assisted microglial replacement in aged animals.
Prof. Loane added: “Furthermore, environmental exposure to acute traumatic brain injury in animals accelerated the age of onset and tissue-wide distribution autofluorescent microglia by increasing oxidative stress damage in the brain of injured animals.”
He continues, “As a result, increasing evidence now suggests that the accumulation of autofluorescent microglia contributes to diseases of aging and neurodegeneration. If these sub-populations of microglia are highly inflammatory and damaging to the brain, then targeting them could be a new strategy for treating aging-related diseases.”
Reference: “Brain injury accelerates the onset of a reversible age-related microglial phenotype associated with inflammatory neurodegeneration” by Rodney M. Ritzel, Yun Li, Yun Jiao, Zhuofan Lei, Sarah J. Doran, Junyun He, Rami A. Shahror, Rebecca J. Henry, Romeesa Khan, Chunfeng Tan, Shaolin Liu, Bogdan A. Stoica, Alan I. Faden, Gregory Szeto, David J. Loane and Junfang Wu, 8 March 2023, Science Advances.
DOI: 10.1126/sciadv.add1101
The study was funded by the National Institutes of Health and Science Foundation Ireland.
Source: SciTechDaily
