Fresh understanding of aging in the brain offers hope for treating neurological diseases

Date:
March 8, 2023
Source:
Trinity College Dublin
Summary:
Scientists 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 unearthed a possible new target for
therapies aimed at treating age-related neurological diseases.


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FULL STORY ========================================================================== Scientists from the Trinity Biomedical Sciences Institute (TBSI)
have shed new light on ageing processes in the brain. By linking the
increased presence of specialised immune cells to conditions such as Alzheimer's disease and traumatic brain injury for the first time, they
have unearthed a possible new target for therapies aimed at treating age-related neurological diseases.


==========================================================================
The research, which benefited from a collaboration with experts at the University of Maryland School of Medicine and focused on microglia in
the brain and spinal cord, is published today in leading international
journal, 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 specialised 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 colour after they have absorbed light of another, and it
occurs because specific substances inside the cells absorb light. The substances stored in specialised 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.

"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.

"As a result, increasing evidence now suggests that the accumulation
of autofluorescent microglia contributes to diseases of ageing 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."
* RELATED_TOPICS
o Health_&_Medicine
# Brain_Tumor # Nervous_System # Immune_System #
Healthy_Aging
o Mind_&_Brain
# Brain_Injury # Neuroscience # Disorders_and_Syndromes
# Dementia
* RELATED_TERMS
o Brain_damage o Traumatic_brain_injury o
Excitotoxicity_and_cell_damage o Alzheimer's_disease o
Urinary_incontinence o Cerebral_contusion o Embryonic_stem_cell
o Stem_cell

========================================================================== Story Source: Materials provided by Trinity_College_Dublin. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. 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, Junfang Wu. Brain injury accelerates the onset of a
reversible age-related microglial phenotype associated with
inflammatory neurodegeneration. Science Advances, 2023; 9 (10)
DOI: 10.1126/ sciadv.add1101 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/03/230308171550.htm

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