Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 7, 2023
Abstract
Underwater
operations
are
widely
used
in
diverse
fields
such
as
marine
exploration,
underwater
construction
and
infrastructure
maintenance,
military
missions.
Previous
research
has
emphasized
the
significance
of
maintaining
cognitive
function
during
these
tasks.
However,
impact
on
underlying
mechanisms
remain
unclear.
Hence,
this
study
aimed
to
investigate
effects
explore
potential
molecular
involved.
We
accomplished
first
by
assessing
operators’
stress
response,
anxiety,
before
after
a
single
operation
two
different
durations
found
that
30
min
improved
while
3
h
induced
significant
decline.
Then,
an
animal
model
swimming
hyperbaric
environment
at
2.0ATA
(atmospheres
absolute)
for
varying
was
applied
simulate
operations.
Behavioral
tests,
histological
examinations,
biochemical
assays
were
conducted,
results
indicated
effect
exercise
time-dependent
prolonged
caused
impairment.
Furthermore,
RNA-sequencing
conducted
normal
control
group
most
significantly
impaired
group,
leading
focus
neuroinflammation
identification
C-C
chemokine
receptor
type
3(CCR3)
target
further
investigation.
Finally,
knockdown
experiment
performed
using
adeno-associated
virus
(AAV)
vector
containing
shRNA
(CCR3)-EGFP
injected
rats’
hippocampus
involvement
CCR3
impairment
exercise.
Results
revealed
alleviated
Moreover,
activated
microglia
promotes
their
polarization
towards
pro-inflammatory
phenotype.
Conversely,
switched
anti-inflammatory
Taken
together,
highlight
shed
insight
alleviating
CCR3-mediated
intervention
targets
protect
brain
Journal of Neuroimmunology,
Год журнала:
2024,
Номер
390, С. 578342 - 578342
Опубликована: Апрель 5, 2024
Alzheimer's
disease
(AD)
is
a
neurodegenerative
characterized
by
cognitive
decline
that
severely
affects
patients
and
their
families.
Genetic
environmental
risk
factors,
such
as
viral
infections,
synergize
to
accelerate
the
aging-associated
neurodegeneration.
factors
for
late-onset
AD
(LOAD),
which
accounts
most
cases,
are
predominantly
implicated
in
microglial
immune
cell
functions.
As
such,
microglia
play
major
role
amyloid
beta
(Aβ)
plaque
(the
pathological
hallmark
of
AD)
formation.
This
review
aims
provide
an
overview
current
knowledge
regarding
Aβ
formation,
well
impact
on
morphological
functional
diversity
plaques.
Based
this
discussion,
we
seek
identify
challenges
opportunities
field
with
potential
therapeutic
implications.
Brain Behavior and Immunity,
Год журнала:
2024,
Номер
119, С. 286 - 300
Опубликована: Апрель 10, 2024
Alzheimer's
disease
is
a
progressive
neurological
disorder
causing
memory
loss
and
cognitive
decline.
The
underlying
causes
of
deterioration
neurodegeneration
remain
unclear,
leading
to
lack
effective
strategies
prevent
dementia.
Recent
evidence
highlights
the
role
neuroinflammation,
particularly
involving
microglia,
in
onset
progression.
Characterizing
initial
phase
can
lead
discovery
new
biomarkers
therapeutic
targets,
facilitating
timely
interventions
for
treatments.
We
used
AppNL-G-F
knock-in
mouse
model,
which
resembles
amyloid
pathology
neuroinflammatory
characteristics
disease,
investigate
transition
from
pre-plaque
an
early
plaque
stage
with
combined
functional
molecular
approach.
Our
experiments
show
decrease
power
cognition-relevant
hippocampal
gamma
oscillations
during
pathology,
together
modification
fast-spiking
interneuron
intrinsic
properties
postsynaptic
input.
Consistently,
transcriptomic
analyses
revealed
that
these
effects
are
accompanied
by
changes
synaptic
function-associated
pathways.
Concurrently,
homeostasis-
inflammatory-related
microglia
signature
genes
were
downregulated.
Moreover,
we
found
Iba1-positive
hippocampus
correlates
aggregation
neuronal
dysfunction.
Collectively,
findings
support
hypothesis
play
protective
stages
preventing
aggregation,
supporting
homeostasis,
overall
preserving
oscillatory
network's
functionality.
These
results
suggest
alteration
dynamics
could
be
pivotal
event
progression
potentially
triggering
deposition,
impairment
interneurons,
breakdown
circuitry
hippocampus.
CNS Neuroscience & Therapeutics,
Год журнала:
2024,
Номер
30(10)
Опубликована: Окт. 1, 2024
Abstract
Background
Inflammatory
and
immune
responses
in
the
brain
that
contribute
to
various
neuropsychiatric
disorders
may
begin
as
microglial
“priming”.
Interferon
(IFN)‐γ
is
known
cause
priming,
but
mechanism
unclear.
Methods
We
examined
effects
of
IFN‐γ
on
gene
expression,
activation,
inflammatory
activity
NLRP3
inflammasome
primary
microglia
brains
mice.
Results
Our
results
showed
treating
cultures
with
induced
a
hedgehog‐like
morphology
upregulated
markers
activation
(CD86,
CD11b)
pro‐inflammatory
molecules
(IL‐1β,
IL‐6,
TNF‐α,
iNOS),
while
downregulating
homeostasis
(CX3CR1,
CD200R1),
anti‐inflammatory
(MCR1,
Arg‐1)
neurotrophic
factors
(IGF‐1,
BDNF).
also
(NLRP3,
caspase‐1,
gasdermin
D,
IL‐18).
This
particular
transcriptional
profiling
makes
IFN‐γ‐primed
exaggerated
upon
lipopolysaccharide
(LPS)
stimulation.
The
level
NLRP3,
IL‐1β,
IL‐18,
TNF‐α
iNOS
treated
both
LPS
were
highest
than
either
one
alone.
Injecting
into
lateral
ventricle
mice
similar
morphological
functional
changes
hippocampal
cultures.
from
or
hippocampus
abolished
when
STAT1
was
inhibited
using
fludarabin.
alone
together
anxiety‐
depression‐like
behaviors
impaired
hippocampus‐dependent
spatial
memory;
these
mitigated
by
Conclusions
primes
activating
STAT1,
which
upregulates
genes
activate
inflammasome.
Inhibiting
IFN‐γ/STAT1
axis
be
way
treat
neurodegenerative
diseases
psychiatric
involve
priming.
Frontiers in Aging Neuroscience,
Год журнала:
2025,
Номер
17
Опубликована: Март 27, 2025
Alzheimer’s
disease
(AD)
is
a
widespread
neurodegenerative
disorder
and
one
of
the
major
challenges
for
public
health.
Despite
extensive
research,
role
microglia
in
AD
remains
complex
dual.
The
aim
this
review
to
summarize
most
recent
advances
research
regarding
dual
concerning
both
immunomodulation
pathological
progression
by
considering
mechanisms
activation
microglia,
effects
on
Aβ
clearance,
tau
pathology,
impacts
due
genetic
variations
microglial
functions.
Among
these
findings
are
status
M1
M2
phenotypes,
crucial
that
variants
like
TREM2
have
modulating
response
microglia.
This
describes
how
modulation
signaling
pathway
might
be
exploited
therapeutically
treatment
underlines
relevance
personalized
medicine
approach.
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Июнь 4, 2025
Abstract
Alzheimer’s
disease
(AD)
is
a
neurodegenerative
disorder
characterized
by
macroscopic
features
such
as
cortical
atrophy,
narrowing
of
the
gyri,
widening
sulci,
and
enlargement
ventricles.
At
cellular
level,
pathological
characteristics
include
extracellular
aggregation
β-amyloid
(Aβ)
forming
senile
plaques,
intracellular
accumulation
hyperphosphorylated
tau
proteins
neurofibrillary
tangles.
AD
leads
to
progressive
decline
cognitive,
behavioral,
social
abilities,
with
no
effective
treatment
available
currently.
The
pathophysiology
complex,
involving
mechanisms
immune
dysregulation
lipid
metabolism
alterations.
Immune
cells,
microglia,
can
identify
clear
aggregates
like
Aβ
early
in
disease.
However,
prolonged
or
excessive
activation
cells
may
trigger
chronic
neuroinflammation,
thereby
accelerating
neuronal
damage
progression
AD.
Lipid
plays
critical
role
maintaining
cell
membrane
structure
function,
regulating
production
clearance
Aβ,
supplying
energy
brain.
Disruptions
these
processes
are
closely
linked
interaction
between
system
further
exacerbates
In
this
review,
we
discuss
response
AD,
summarize
their
intricate
interactions,
highlight
complexity
multifactorial
pathogenic
cascade,
offering
insights
into
new
interventions
targeting
immune-metabolic
axis
