European Journal of Neuroscience,
Journal Year:
2024,
Volume and Issue:
60(1), P. 3629 - 3642
Published: May 2, 2024
Abstract
Microglia
are
endogenous
immune
cells
in
the
brain,
and
their
pyroptosis
phenotype
dichotomy
proved
to
play
roles
neurodegenerative
diseases.
We
investigated
whether
how
hypoxia
affected
polarization
mouse
microglia.
Primary
microglia
BV2
were
exposed
hypoxia.
Pyroptosis
M1/M2
assessed
by
measuring
gasdermin
D
truncation
surface
marker
expression.
Mechanisms
including
purinergic
ionotropic
receptor
(P2XR),
peroxisome
proliferator‐activated
coactivator‐1α
(PGC‐1α)
NOD‐like
protein
3
(NLRP3)
inflammasome
investigated.
reported
(90%
N
2
,
5%
O
CO
)
induced
promoted
M1
primary
microglia,
effect
appeared
after
6
h
exposure.
Although
h)
had
no
on
P2X1R
P2X7R
expression,
it
increased
P2X4R
expression
decreased
PGC‐1α
Interestingly,
blockade
of
or
abolished
hypoxia‐modulated
polarization.
overexpression
overactivation
alleviated
hypoxia‐induced
polarization,
while
knockdown
deactivation
under
normoxic
situation.
Further,
NLRP3
activated
caspase‐1
phosphorylation
NF‐κB
reduced
STAT3/6.
inhibitor
pyroptosis,
STAT
inducer
ameliorated
In
addition,
activator
STAT3/6
caused
concluded
cultured
may
induce
via
P2XR/PGC‐1α/NLRP3/caspase‐1
pathway
trigger
through
P2XR/PGC‐1α/NF‐κB/STAT3/6
pathway.
Abstract
Background
Depression
is
a
serious
mental
disorder
and
the
most
prevalent
cause
of
disability
suicide
worldwide.
Chronic
unpredictable
mild
stress
(CUMS)
can
lead
to
significant
acceleration
depression
development.
Quercetin
(Que)
flavonoid
compound
with
wide
range
pharmacological
effects.
Recent
studies
have
shown
that
quercetin
improve
CUMS‐induced
depression‐like
behavior,
but
mechanism
its
improvement
still
unclear.
α2δ‐1
regulatory
subunit
voltage‐gated
calcium
channel,
which
interact
N‐methyl‐D‐aspartate
receptor
(NMDAR)
form
complex.
Objective
In
this
study,
we
found
Que
could
inhibit
increase
NMDAR
expression
in
rat
hypothalamus
induced
by
CUMS.
pain,
chronic
hypertension
other
interacts
complex,
subsequently
affects
level
NMDAR.
Consequently,
present
study
aimed
investigate
antidepressant
effect
vivo
vitro
explore
action
terms
interaction
between
Methods
Rats
were
randomly
exposed
two
stressors
every
day
for
4
weeks
establish
CUMS
model,
then
sucrose
preference
test
(SPT),
forced
swimming
(FST),
tail
suspension
(TST),
open
field
(OFT)
performed
detect
behavior
rats,
so
as
evaluate
whether
model
was
successfully
established
on
rats.
Experimental
techniques
such
serum
enzyme‐linked
immunosorbent
assay
(ELISA),
immunofluorescence,
Western
blot,
co‐immunoprecipitation,
well
experiments,
used
mechanisms
exerts
Results
Behavioral
ELISA
results
showed
produce
reduction
excitability
hypothalamic–pituitary–adrenal
(HPA)
axis
rats
improvements
their
depressive
behavior.
co‐immunoprecipitation
experiments
produced
decrease
NMDAR1
levels
interfered
binding.
addition,
neural
regulation
PC12
cells
knocked
out
gene
further
verified.
Cellular
demonstrated
led
reversal
up‐regulation
corticosterone‐injured
cells,
while
had
no
effects
knockout.
Conclusions
has
good
significantly
caused
It
inhibiting
α2δ‐1,
interfering
NMDAR,
reducing
HPA
axis.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Feb. 5, 2024
Background:
The
Jiawei
Kongsheng
Zhenzhong
pill
(JKZP),
a
Chinese
herbal
prescription
comprised
of
eight
crude
drugs,
has
been
historically
employed
to
treat
neurological
and
psychological
disorders.
Nevertheless,
the
ambiguous
material
basis
severely
hindered
its
progress
application.
Purpose:
current
study
aimed
establish
rapid
analytical
method
for
identifying
chemical
components
JKZP
aqueous
extract
absorbed
into
rat
serum
investigate
quality
markers
(Q-markers)
responsible
neuroprotective
effects
JKZP.
Methods:
qualitative
detection
components,
prototype
metabolites
extracts
JKZP,
as
well
samples
rats
that
were
administered
drug,
was
performed
using
ultra-performance
liquid
chromatography-
quadrupole
time-of-flight
tandem
mass
spectrometry
(UPLC-Q-TOF-MS/MS)
technology.
This
analysis
combined
information
from
literature
reports
database
comparisons.
Moreover,
conducted
anticipate
potential
Q-markers
based
on
“five
principles”
Q-marker
determination.
Results:
A
total
67
compounds
111
(comprising
33
prototypes
78
metabolites)
detected
identified.
Combining
principles
transmission
traceability,
compound
compatibility
environment,
component
specificity,
effectiveness,
measurability,
predicted
five
key
compounds,
namely,
senkyunolide
H,
danshensu,
echinacoside,
loganin,
3,6′-disinapoyl
sucrose,
may
serve
pharmacological
bases
Conclusion:
To
summarize,
UPLC-Q-TOF-MS/MS
technique
can
be
rapidly
accurately
identify
in
Five
active
have
discovery
serves
reference
improving
quality,
advancing
further
research
development,
utilizing
prescriptions.
Frontiers in Pharmacology,
Journal Year:
2023,
Volume and Issue:
14
Published: June 13, 2023
Microglial
activation-induced
neuroinflammation
is
closely
related
to
the
development
of
sepsis-associated
encephalopathy.
Accumulating
evidence
suggests
that
changes
in
metabolic
profile
microglia
crucial
for
their
response
inflammation.
Propofol
widely
used
sedation
mechanically
ventilated
patients
with
sepsis.
Here,
we
investigate
effect
propofol
on
lipopolysaccharide-induced
neuroinflammation,
neuronal
injuries,
reprogramming
as
well
underlying
molecular
mechanisms.
The
neuroprotective
effects
(80
mg/kg)
vivo
were
measured
lipopolysaccharide
(2
mg/kg)-induced
sepsis
mice
through
behavioral
tests,
Western
blot
analysis
and
immunofluorescent
staining.
anti-inflammatory
(50
μM)
microglial
cell
cultures
under
(10
ng/ml)
challenge
examined
Seahorse
XF
Glycolysis
Stress
test,
ROS
assay,
blot,
We
showed
treatment
reduced
activation
inhibited
apoptosis
improved
cognitive
dysfunction.
also
attenuated
lipopolysaccharide-stimulated
increases
inducible
nitric
oxide
synthase,
oxide,
tumor
necrosis
factor-α,
interlukin-1β
COX-2
cultured
BV-2
cells.
Propofol-treated
a
remarkable
suppression
HIF-1α,
PFKFB3,
HK2
expression
along
downregulation
ROS/PI3K/Akt/mTOR
signaling
pathway.
Moreover,
enhancement
mitochondrial
respiration
glycolysis
induced
by
lipopolysaccharide.
Together,
our
data
suggest
inflammatory
inhibiting
reprogramming,
at
least
part,
ROS/PI3K/Akt/mTOR/HIF-1α
Frontiers in Neuroscience,
Journal Year:
2025,
Volume and Issue:
18
Published: Jan. 8, 2025
In
recent
years,
depression
has
become
a
global
public
health
concern,
and
one
of
the
common
concomitant
symptoms
are
diminished
sexual
motivation
impaired
performance.
The
aim
this
study
was
to
investigate
potential
effects
Morinda
officinalis
oligosaccharides
(MOO)
on
its
symptom,
dysfunction.
Chronic
unpredictable
mild
stress
(CUMS)-induced
model
constructed,
MOO
abilities
were
evaluated.
results
revealed
that
able
alleviate
CUMS-induced
depression-like
behavior
in
mice,
inhibit
hippocampal
neuron
apoptosis,
reverse
monoamine
neurotransmitter
imbalance,
increase
Brain-derived
neurotrophic
factor
(BDNF)
expression
levels
hippocampus,
modulate
composition
distribution
gut
microbiota,
abundance
probiotics
after
continuous
gavage
for
28
days.
further
confirmed
dysfunction
is
closely
related
development
by
improving
lack
low
performance
depressed
modulating
disruption
sex
hormone
secretion
serum,
alleviating
sperm
morphology
functional
defects
epididymis.
These
findings
provide
basis
exploring
antidepressant
mechanism,
use
improve
hypogonadotropic
symptoms,
future
new
drug
improves
symptoms.
