Summary: As the brain ages, microglia enter dysfunctional states that increase the risk of developing neurodegenerative diseases such as Alzheimer’s disease.
Source: DCT
Scientists from the Trinity Biomedical Sciences Institute (TBSI) have shed new light on aging processes in the brain. By linking the increased presence of specialized immune cells to conditions such as Alzheimer’s disease and traumatic brain injury for the first time, they have uncovered a possible new target for therapies aimed at treating age-related neurological diseases. .
The research, which benefited from a collaboration with experts from the University of Maryland School of Medicine and focused on microglia in the brain and spinal cord, is published today in the leading international journal , Scientific advances.
Microglia are a unique type of immune cell whose job is to support nerve cells, defend against invading microbes, clear debris, and eliminate dying nerve cells by engulfing and eating them. Emerging research indicates that microglia may have different functional responses depending on the molecular and biochemical changes that occur within these specialized cells.
In fact, various subtypes of microglia can be distinguished based on a property called autofluorescence. It is the tendency of cells to emit light of one color after absorbing light of another, and it occurs because specific substances inside cells absorb light. Substances stored in specialized cellular compartments include fat molecules, cholesterol crystals, metals, and other misfolded proteins.
David Loane, assistant professor of neuroscience in the Trinity School of Biochemistry and Immunology at TBSI is the lead author of the research. He said:
“As the brain ages, these materials build up inside the autofluorescent microglia, increasing their autofluorescence as a result. Unfortunately, this buildup of cellular debris also makes it harder for the microglia to perform its essential tasks of collecting garbage in the brain and preventing neurological damage and neurodegenerative diseases.
“In this study, we found – in aged animals – that these microglia adopt a uniquely dysfunctional state, which has a number of problematic impacts. For example, there is an increase in stress and cell damage, an accumulation of fats and iron, alterations in metabolic processes and an increase in the production of molecules that overload the immune response.
Additionally, the scientists demonstrated that autofluorescent microglia and associated inflammation were more pronounced in pathological conditions, such as in genetic risk factor models of Alzheimer’s disease, and – promisingly – were reversed by the Drug-assisted microglial replacement in aged animals.
Professor Loane added:
“Furthermore, environmental exposure to acute traumatic brain injury in animals accelerated the age of onset and tissue-wide distribution of autofluorescent microglia by increasing oxidative stress damage in the brain. injured animals.
“As a result, growing evidence now suggests that autofluorescent microglia accumulation contributes to diseases of aging and neurodegeneration. If these microglia subpopulations are highly inflammatory and brain damaging, then targeting them could be a new strategy to treat age-related diseases.
About this aging and neuroscience research news
Author: Thomas Dean
Source: DCT
Contact: Thomas Deane – TCD
Picture: Image is in public domain
Original research: Free access.
“Brain injury accelerates the onset of a reversible age-related microglial phenotype associated with inflammatory neurodegeneration” by David Loane et al. Scientists progress
Abstract
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Brain injury accelerates onset of reversible age-related microglial phenotype associated with inflammatory neurodegeneration
Lipofuscin is an autofluorescent (AF) pigment formed from lipids and misfolded proteins, which accumulates in postmitotic cells with advanced age.
Here, we immunophenotyped microglia in the brains of old C57BL/6 mice (>18 months) and demonstrated that compared to young mice, one-third of old microglia are AF, characterized by profound changes in lipid content and iron, phagocytic activity, and oxidative stress.
Pharmacological depletion of microglia in aged mice eliminated AF microglia after repopulation and reversed microglial dysfunction.
Age-related neurological deficits and neurodegeneration after traumatic brain injury (TBI) were attenuated in aged mice lacking AF microglia.
Moreover, increased phagocytic activity, lysosomal load and lipid accumulation in microglia persisted up to 1 year after TBI, were modified by APOE4 genotype, and chronically driven by phagocyte-mediated oxidative stress.
Thus, AF may reflect a disease state in aging microglia associated with increased phagocytosis of neurons and myelin and inflammatory neurodegeneration that may be further accelerated by TBI.