Journal of Alzheimer s Disease,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 2, 2025
Alzheimer's
disease
(AD)
is
characterized
by
deposition
of
amyloid-β
(Aβ)
and
neurofibrillary
tangles
(NFTs)
formed
aggregates
hyperphosphorylated
tau
proteins.
It
presents
a
formidable
global
health
challenge,
prompting
the
exploration
innovative
therapeutic
strategies.
This
review
aims
to
provide
thorough
discussion
astrocytes
microglia
examine
whether
they
are
overall
beneficial
or
detrimental
for
AD
on
level.
Based
this,
this
describes
treatment
solutions
that
likely
entail
manipulation
glial
cells
reduce
inflammation,
opting
boost
clearance
toxic
proteins,
thus
stabilizing
effects
AD.
These
entities,
inherent
central
nervous
system,
extend
their
functions
beyond
structural
support,
actively
engaging
in
various
physiological
pathological
processes
associated
with
Both
astroglia
contribute
significantly
neuroinflammatory
response
observed
Reactive
release
inflammatory
mediators,
while
activated
cytokines,
chemokines,
reactive
oxygen
species,
collectively
assisting
chronic
state
neuroinflammation.
Additionally,
partake
Aβ,
play
pivotal
role
phagocytosing
Aβ
plaques.
In
AD,
ongoing
inflammation
may
cause
buildup
which
causes
problems
also
worsens
these
issues
communication
between
neurons,
key
factor
cognitive
decline.
addition,
there
tremendous
opportunities
identify
new
biomarkers
specific
disorders,
genomic
epigenomic
approaches
selection
patients,
using
multimodal
imaging
techniques,
application
machine
learning
algorithms
future
personalized
glial-targeted
therapies.
Cell Reports Medicine,
Год журнала:
2024,
Номер
5(5), С. 101522 - 101522
Опубликована: Май 1, 2024
Neuroinflammation
plays
a
significant
role
in
ischemic
injury,
which
can
be
promoted
by
oxidized
mitochondrial
DNA
(Ox-mtDNA).
Cytidine/uridine
monophosphate
kinase
2
(CMPK2)
regulates
mtDNA
replication,
but
its
neuroinflammation
and
injury
remains
unknown.
Here,
we
report
that
CMPK2
expression
is
upregulated
monocytes/macrophages
microglia
post-stroke
humans
mice,
respectively.
Microglia/macrophage
knockdown
using
the
Cre
recombination-dependent
adeno-associated
virus
suppresses
inflammatory
responses
brain,
reduces
infarcts,
improves
neurological
outcomes
CX3CR1Cre/ERT2
mice.
Mechanistically,
limits
newly
synthesized
Ox-mtDNA
formation
subsequently
blocks
NLRP3
inflammasome
activation
microglia/macrophages.
Nordihydroguaiaretic
acid
(NDGA),
as
inhibitor,
discovered
to
reduce
mice
prevent
primary
human
monocytes
from
patients.
Thus,
these
findings
identify
promising
therapeutic
target
for
stroke
other
brain
disorders
associated
with
neuroinflammation.
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Фев. 21, 2025
Sepsis-associated
encephalopathy
(SAE)
is
a
severe
neurological
condition
caused
by
sepsis,
and
presents
with
symptoms
ranging
from
delirium
coma
to
long-term
cognitive
dysfunction.
SAE
acknowledged
as
widespread
brain
impairment
characterized
the
activation
of
microglia.
However,
specific
pathological
mechanisms
that
drive
this
are
still
not
clearly
understood.
Growth
differentiation
factor
15
(GDF15)
levels
have
been
noted
be
considerably
increased
in
patients
where
they
linked
disease
severity
can
independently
predict
short-
mortality
risk.
Serum
GDF15
also
negatively
associated
gray
matter
volume
older
individuals.
impact
on
sepsis-induced
memory
impairments,
well
behind
these
effects,
poorly
To
examine
role
SAE,
sepsis
model
was
created
adult
C57BL/6J
mice
using
intraperitoneal
administration
lipopolysaccharide
(LPS).
plasma
cerebrospinal
fluid
were
measured
ELISA.
The
anti-GDF15
monoclonal
antibody
ponsegromab
injected
intracerebroventricularly
before
modeling,
functions
septic
assessed
fear-conditioning
novel
object
recognition
tests.
Microglial
phagocytosis
evaluated
immunofluorescence
Golgi
staining.
Additionally,
an
vitro
investigation
LPS-stimulated
microglia
conducted
evaluate
impacts
inflammatory
cytokine
productions
microglial
phagocytic
activity.
Mechanisms
explored
RNA
sequencing,
qPCR,
western
blotting,
flow
cytometry,
assays.
In
mice,
notably
elevated
after
injection
LPS.
Lateral
ventricular
alleviated
both
together
hippocampus,
thereby
protecting
against
synaptic
loss.
brains
mice.
Targeting
found
improve
reducing
response
phagocytosis.
These
results
indicate
could
serve
important
therapeutic
target
for
treating
SAE.
Microglia
actively
survey
the
brain
and
dynamically
interact
with
neurons
to
maintain
homeostasis.
Microglial
Gi
protein–coupled
receptors
(Gi-GPCRs)
play
a
critical
role
in
microglia-neuron
communications.
However,
impact
of
temporally
activating
microglial
signaling
on
dynamics
neuronal
activity
homeostatic
remains
largely
unknown.
In
this
study,
we
used
Gi-based
designer
exclusively
activated
by
drugs
(Gi-DREADD)
selectively
modulate
pathway.
By
integrating
chemogenetic
approach
vivo
two-photon
imaging,
observed
that
exogenous
activation
transiently
inhibited
process
dynamics,
reduced
activity,
impaired
synchronization.
These
altered
functions
were
associated
decrease
interactions
between
microglia
neuron
somata.
Together,
study
demonstrates
acute,
regulates
circuit
function,
offering
potential
pharmacological
target
for
neuromodulation
through
microglia.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 2, 2025
Pregnancy
involves
complex
physiological
adaptations
across
maternal
organs
and
the
immune
system
to
support
fetal
development.
Macrophages
play
a
dual
role
during
pregnancy:
defending
against
pathogens
supporting
tissue
adaptation.
However,
comprehensive
in-depth
studies
of
cross-tissue
transcriptional
heterogeneity
macrophages
healthy
pregnancy
at
single-cell
level
remain
elusive.
We
performed
RNA
sequencing
(scRNA-seq)
profile
from
pregnant
pig
49
tissues.
Immunofluorescence
was
verify
specific
expression
transcription
factors.
In
this
study,
we
generated
macrophage
atlas
containing
114,881
tissues/organs
within
one
single
pig,
identified
33
subtypes,
revealed
extensive
tissue-specific
diversity.
observed
significant
subtypes
five
different
anatomical
sites
adipose
tissue.
Notably,
Mφ
MARCO+
subtype,
primarily
derived
mesenteric
tissue,
showed
higher
activity
in
pattern
recognition
receptor
signaling
pathways
compared
other
tissues,
including
fat
depots.
Cross-tissue
analysis
distinct
patterns
factors,
cytokines,
cell
surface
receptors,
factor
PLSCR1,
specifically
expressed
lung
verified
by
immunofluorescence.
Cross-species
unveiled
conservation
among
pigs,
humans,
mice.
constructed
multiple-tissue
transcriptome
revealing
their
molecular
differences
commonalities
tissues
species.
Our
study
provides
valuable
resource
for
understanding
diversity
pigs.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 2, 2024
Abstract
Motor
cortical
hyperexcitability
is
well-documented
in
the
presymptomatic
stage
of
amyotrophic
lateral
sclerosis
(ALS).
However,
mechanisms
underlying
this
early
dysregulation
are
not
fully
understood.
Microglia,
as
principal
immune
cells
central
nervous
system,
have
emerged
important
players
sensing
and
regulating
neuronal
activity.
Here
we
investigated
role
microglia
motor
circuits
a
mouse
model
TDP-43
neurodegeneration
(rNLS8).
Utilizing
multichannel
probe
recording
longitudinal
vivo
calcium
imaging
awake
mice,
observed
hyperactivity
at
initial
disease
progression.
Spatial
single-cell
RNA
sequencing
revealed
that
primary
responders
to
hyperactivity.
We
further
identified
unique
subpopulation
microglia,
rod-shaped
which
characterized
by
distinct
morphology
transcriptional
profile.
Notably,
predominantly
interact
with
dendrites
excitatory
synaptic
inputs
attenuate
The
elimination
through
TREM2
deficiency
increased
hyperactivity,
exacerbated
deficits,
decreased
survival
rates
rNLS8
mice.
Together,
our
results
suggest
play
neuroprotective
attenuating
related
neurodegeneration.
Molecular Neurobiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 14, 2024
Abstract
Neural
circuits
consisting
of
neurons
and
glial
cells
help
to
establish
all
functions
the
CNS.
Microglia,
resident
immunocytes
CNS,
are
endowed
with
UDP-sensitive
P2Y6
receptors
(P2Y6Rs)
which
regulate
phagocytosis/pruning
excessive
synapses
during
individual
development
refine
in
an
activity-dependent
manner
adulthood.
In
addition,
this
type
receptor
plays
a
decisive
role
primary
(Alzheimer’s
disease,
Parkinson’s
neuropathic
pain)
secondary
(epilepsy,
ischemic-,
mechanical-,
or
irradiation-induced)
neurodegeneration.
A
whole
range
microglial
cytokines
controlled
by
P2Y6Rs,
such
as
interleukins
IL-1β,
IL-6,
IL-8,
tumor
necrosis
factor-α
(TNF-α),
leads
neuroinflammation,
resulting
Hence,
small
molecular
antagonists
P2Y6Rs
genetic
knockdown
provide
feasible
ways
alleviate
inflammation-induced
neurological
disorders
but
might
also
interfere
regulation
synaptic
circuitry.
The
present
review
aims
at
investigating
dual
microglia,
both
shaping
neural
targeted
phagocytosis
promoting
neurodegenerative
illnesses
fostering
neuroinflammation
through
multiple
transduction
mechanisms.
Brain Behavior & Immunity - Health,
Год журнала:
2025,
Номер
43, С. 100933 - 100933
Опубликована: Янв. 5, 2025
Early
life
stress
(ELS)
has
lasting
consequences
on
microglia
and
brain
macrophage
function.
During
ELS,
macrophages
alter
their
engagement
with
synapses
leading
to
changes
in
neuronal
excitability.
Further,
ELS
can
induce
innate
immune
memory
formation
resulting
altered
responsivity
future
environmental
stimuli.
These
alterations
result
adaptations
circuit
function
may
mediate
the
relationship
between
risk
develop
alcohol
use
disorder
(AUD).
Whether
truly
this
remains
elusive.
Here,
we
report:
1)
an
model,
psychosocial
(PSS),
increases
binge-like
ethanol
consumption
early
adulthood.
2)
Repeated
population
densities
across
brain.
3)
PSS
elicit
following
repeated
consumption.
4)
Microglia
inhibition
trended
towards
preventing
PSS-evoked
normalized
densities.
Therefore,
our
study
suggests
that
acutely
inhibiting
during
periods
of
prevent
assist
reducing
AUD.
