Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 3, 2023
Abstract
Background
NLRP3
inflammasome
activation
is
critical
for
neuroinflammation
in
microglia
during
postoperative
cognitive
dysfunction
(POCD)
induced
by
sevoflurane.
However,
the
molecular
mechanism
which
sevoflurane
activates
remains
unclear.
The
cGAS-
STING
pathway
an
evolutionarily
conserved
inflammatory
defense
mechanism.
role
of
cGAS-STING
sevoflurane-induced
inflammasome-dependent
and
underlying
mechanisms
require
further
investigation.
Methods
Prolonged
anesthesia
with
was
used
to
induce
mice.
passive
avoidance
test
Y-maze
were
assess
function.
We
then
cGAS
inhibitor
RU.521
investigate
whether
involved
mice
microglia.
To
sevoflurane-treated
microglia,
we
pre-treated
Mdivi-1
(a
DRP1
inhibitor),
CsA
mPTP
inhibitor)
or
VBIT-4
VDAC
inhibitor).
Results
found
that
prolonged
triggered
characterized
inflammasome.
Interestingly,
activated
hippocampus
receiving
While
blockade
attenuated
In
vitro
,
treatment
significantly
while
pre-treatment
robustly
inhibited
activation.
Mechanistically,
mitochondrial
fission
released
DNA
(mtDNA)
into
cytoplasm,
could
be
abolished
Mdivi-1.
Blocking
mtDNA
release
via
mPTP-VDAC
channel
cytosolic
escape
reduced
finally
inhibiting
Conclusion
this
study,
reported
a
novel
POCD.
Therefore,
regulating
targeting
may
provide
therapeutic
target
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Окт. 30, 2024
This
study
investigated
the
role
of
mitochondrial
dynamics
in
postoperative
cognitive
dysfunction
(POCD)
and
assessed
therapeutic
potential
modulation,
particularly
through
inhibition
dynamin-related
protein
1
(DRP1)
with
Mdivi-1.
Our
findings
indicated
that
DRP1
substantially
mitigated
neuroinflammation
mediated
by
microglial
cells,
contributing
to
improved
function
POCD
models.
The
administration
Mdivi-1
led
a
notable
decrease
fission,
reduced
reactive
oxygen
species
(ROS)
production,
stabilization
membrane
potential,
all
which
correlate
diminished
neuroinflammation,
as
evidenced
lower
NOD-like
receptor
family
pyrin
domain
containing
3
(NLRP3)/
interleukin-1β
(IL-1β)
expression
cells.
Importantly,
treatment
was
also
found
enhance
synaptic
plasticity,
increasing
spine
density
hippocampal
region
mice.
improvement
health
integrity
paralleled
enhanced
performance,
demonstrated
Y-maze
tests.
These
results
underscored
critical
pathophysiology
suggested
targeting
dysfunction,
specifically
inhibition,
could
be
an
effective
approach
for
treatment.
Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 3, 2023
Abstract
Background
NLRP3
inflammasome
activation
is
critical
for
neuroinflammation
in
microglia
during
postoperative
cognitive
dysfunction
(POCD)
induced
by
sevoflurane.
However,
the
molecular
mechanism
which
sevoflurane
activates
remains
unclear.
The
cGAS-
STING
pathway
an
evolutionarily
conserved
inflammatory
defense
mechanism.
role
of
cGAS-STING
sevoflurane-induced
inflammasome-dependent
and
underlying
mechanisms
require
further
investigation.
Methods
Prolonged
anesthesia
with
was
used
to
induce
mice.
passive
avoidance
test
Y-maze
were
assess
function.
We
then
cGAS
inhibitor
RU.521
investigate
whether
involved
mice
microglia.
To
sevoflurane-treated
microglia,
we
pre-treated
Mdivi-1
(a
DRP1
inhibitor),
CsA
mPTP
inhibitor)
or
VBIT-4
VDAC
inhibitor).
Results
found
that
prolonged
triggered
characterized
inflammasome.
Interestingly,
activated
hippocampus
receiving
While
blockade
attenuated
In
vitro
,
treatment
significantly
while
pre-treatment
robustly
inhibited
activation.
Mechanistically,
mitochondrial
fission
released
DNA
(mtDNA)
into
cytoplasm,
could
be
abolished
Mdivi-1.
Blocking
mtDNA
release
via
mPTP-VDAC
channel
cytosolic
escape
reduced
finally
inhibiting
Conclusion
this
study,
reported
a
novel
POCD.
Therefore,
regulating
targeting
may
provide
therapeutic
target
