Psychiatry and Clinical Neurosciences,
Год журнала:
2024,
Номер
78(9), С. 517 - 526
Опубликована: Июль 16, 2024
Background
Systemic
infections
are
associated
with
the
development
of
AD,
especially
in
individuals
carrying
APOE4
genotype.
However,
detailed
mechanism
through
which
affects
microglia
inflammatory
response
remains
unclear.
Methods
We
obtained
human
snRNA‐seq
data
from
Synapse
AD
Knowledge
Portal
and
assessed
DEGs
between
APOE3
isoforms
microglia.
To
verify
interaction
ApoE
infectious
products,
we
used
to
stimulate
vitro
vivo
models
presence
or
absence
LPS
(or
ATP).
The
NLRP3
gene
knockout
experiment
was
performed
demonstrate
whether
APOE‐NLRP3
axis
indispensable
for
regulate
inflammation
mitochondrial
autophagy.
Results
were
evaluated
by
biochemical
analyses
fluorescence
imaging.
Compared
APOE3,
up‐regulated
genes
carriers
involved
pro‐inflammatory
responses.
ApoE4‐stimulation
significantly
increased
levels
inflammasomes
ROS
Moreover,
compared
ApoE4
alone,
co‐incubation
ATP)
markedly
promoted
pyroptosis.
Both
NF‐κB
activation
autophagy
dysfunction
contributed
level
induced
ApoE4.
Furthermore,
pathological
impairment
could
be
reversed
KO.
Conclusions
Our
study
highlights
importance
linking
innate
immune
function.
These
findings
not
only
provide
a
molecular
basis
APOE4‐mediated
neuroinflammatory
but
also
reveal
potential
reason
risk
after
contracting
diseases.
The Journal of Headache and Pain,
Год журнала:
2024,
Номер
25(1)
Опубликована: Янв. 5, 2024
Abstract
Background
Neuroinflammation,
mediated
by
the
activation
of
microglia,
contributes
to
central
sensitization,
which
is
associated
with
development
chronic
migraine
(CM).
TREM1
receptors
amplify
inflammatory
response.
However,
their
relationship
CM
unclear.
Thus,
this
study
endeavoured
elucidate
exact
role
in
CM.
Methods
Nitroglycerin
(NTG)
was
repeatedly
administered
intraperitoneally
establish
model.
Mechanical
and
thermal
sensitivities
were
assessed
using
von
Frey
filaments
hot
plate
assays.
Using
Western
blotting,
TREM1,
NF-κB
pathway,
NLRP3
inflammasome
components,
proinflammatory
cytokines
all
detected.
Immunofluorescence
used
examine
cellular
distribution
NLRP3,
number
immunoreactivity,
morphological
changes.
We
examined
effects
antagonists
(LR12)
inhibitors
(PDTC)
on
pain
behaviour,
as
well
production
c-fos
CGRP.
Additionally,
we
investigated
whether
LR12
PDTC
affect
microglia
inflammasome.
synthesized
siRNA
TREM1-overexpressing
plasmids
transfect
BV2
cells
treated
LPS
normal
PDTC.
The
quantified
blotting.
Results
Following
NTG
administration,
expression
significantly
upregulated
exclusively
localized
TNC,
co-localized
NLRP3.
Furthermore,
classical
pathway
observed.
Pre-treatment
effectively
attenuated
mechanical
hypersensitivity,
suppressed
CGRP,
inhibited
activity
mice.
inhibition
mitigated
NTG-induced
activation,
production.
In
vitro,
knockdown
resulted
following
lipopolysaccharide
(LPS)
treatment
reduced
components
cytokines.
After
overexpression,
activated,
upregulated,
reversed
phenomenon.
Conclusions
Our
findings
suggest
that
regulates
via
thereby
contributing
sensitization
implicating
its
involvement
pathogenesis.
Abstract
Background
Neuropathic
pain
is
chronic
and
has
few
effective
control
strategies.
Studies
have
demonstrated
that
microRNAs
functions
in
neuropathic
pain.
However,
no
study
been
conducted
to
demonstrate
the
role
mechanism
of
microRNA
(miR)-31-5p
Accordingly,
this
sought
determine
pathological
miR-31-5p
constriction
injury
(CCI)
-induced
mouse
models.
Methods
We
used
CCI
surgery
establish
model.
Behavioral
tests
were
performed
evaluate
sensitivity
mice.
Expressions
inflammatory
cytokines
dorsal
root
ganglion
(DRG)
examined
by
polymerase
chain
reaction.
Animals
or
cells
received
with/without
mimic
inhibitor
investigate
its
The
was
assayed
using
western
blotting,
immunofluorescence
staining
dual-luciferase
reporter
assay.
Results
found
led
a
significant
decrease
levels.
Knockout
administration
miPEP31
exacerbated
C57BL/6
Meanwhile,
overexpression
increased
paw
withdrawal
threshold
latency.
TRAF6
one
target
gene
miR-31-5p,
which
can
trigger
complex
response.
associated
with
reducing
DRG
expression
could
alleviate
In
addition,
inhibited
reduced
neuroinflammatory
Conclusions
All
results
reveal
potentially
models
inhibiting
mediated
MiR-31-5p
upregulation
highlighted
here
as
new
for
treatment.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 3805 - 3805
Опубликована: Март 29, 2024
The
post-COVID
condition
(PCC)
is
a
pathology
stemming
from
COVID-19,
and
studying
its
pathophysiology,
diagnosis,
treatment
crucial.
Neuroinflammation
causes
the
most
common
manifestations
of
this
disease
including
headaches,
fatigue,
insomnia,
depression,
anxiety,
among
others.
Currently,
there
are
no
specific
management
proposals;
however,
given
that
inflammatory
component
involves
cytokines
free
radicals,
these
conditions
must
be
treated
to
reduce
current
symptoms
provide
neuroprotection
risk
long-term
neurodegenerative
disease.
It
has
been
shown
cannabis
compounds
with
immunomodulatory
antioxidant
functions
in
other
pathologies.
Therefore,
exploring
approach
could
viable
therapeutic
option
for
PCC,
which
purpose
review.
This
review
involved
an
exhaustive
search
specialized
databases
PubMed,
PubChem,
ProQuest,
EBSCO,
Scopus,
Science
Direct,
Web
Science,
Clinical
Trials.
Phytocannabinoids,
cannabidiol
(CBD),
cannabigerol
(CBG),
Delta-9-tetrahydrocannabinol
(THC),
exhibit
significant
antioxidative
anti-inflammatory
properties
have
effective
neuroinflammatory
conditions.
These
promising
adjuvants
PCC
alone
or
combination
antioxidants
therapies.
presents
challenges
neurological
health,
neuroinflammation
oxidative
stress
play
central
roles
pathogenesis.
Antioxidant
therapy
cannabinoid-based
approaches
represent
areas
research
mitigating
adverse
effects,
but
further
studies
needed.
Cells,
Год журнала:
2023,
Номер
12(23), С. 2672 - 2672
Опубликована: Ноя. 21, 2023
Alzheimer’s
disease
(AD)
is
a
leading
neurodegenerative
condition
causing
cognitive
and
memory
decline.
With
small-molecule
drugs
targeting
Aβ
proving
ineffective,
alternative
targets
are
urgently
needed.
Neuroinflammation,
which
central
to
AD’s
pathology,
results
in
synaptic
neuronal
damage,
highlighting
the
importance
of
addressing
inflammation
conserving
integrity.
Cannabidiol
(CBD),
derived
from
cannabis,
noted
for
its
neuroprotective
anti-inflammatory
properties,
having
shown
efficacy
neuropathic
pain
management
epilepsy.
To
investigate
therapeutic
CBD
AD
elucidate
underlying
mechanisms,
we
aimed
contribute
valuable
insights
incorporating
prevention
recommendations
into
future
nutritional
guidelines.
Aβ1–42
was
employed
vivo
or
vitro
model
establishment,
treatment
utilized
assess
CBD,
RNA-seq
analysis
conducted
mechanism.
mitigates
Aβ-induced
deficits
by
modulating
microglial
activity,
promoting
neurotrophic
factor
release,
regulating
inflammatory
genes.
The
administration
demonstrated
protective
effect
against
toxicity
both
vivo,
along
with
an
amelioration
impairment
mice.
These
findings
support
potential
inclusion
guidelines
prevention.
Cannabis and Cannabinoid Research,
Год журнала:
2023,
Номер
9(3), С. 797 - 808
Опубликована: Ноя. 17, 2023
Background:
Status
epilepticus
(SE)
is
a
series
of
seizures
that
can
lead
to
serious
neurological
damages.
Cannabidiol
(CBD)
extracted
from
the
cannabis
plant,
which
has
been
approved
as
an
antiseizure
medication.
This
study
aimed
determine
efficacy
various
doses
CBD
on
lithium-pilocarpine-induced
SE
in
rats
and
possible
involvement
multiple
pharmacological
pathways.
We
hypothesized
cannabinoid
receptors
type
1
(CB1)
CB2,
well
GABAA
receptors,
might
have
important
roles
anticonvulsant
effects
against
by
its
anti-inflammatory
effects.
Methods:
was
induced
intraperitoneal
(i.p.)
injection
lithium
(127
mg/kg,
i.p.)
pilocarpine
(60
i.p.,
20
h
after
lithium).
Forty-two
male
were
divided
into
seven
groups
(including
control
sham
groups),
treated
received
different
(1,
3,
5,
10,
25
i.p.).
score
recorded
over
next
2
following
injection.
Then,
we
measured
levels
pro-inflammatory
cytokines,
including
interleukin
(IL)-lβ
tumor
necrosis
factor
(TNF)-α,
using
ELISA
kits.
Also
analyzed
expression
CB1,
Western
blot
technique.
Results:
at
5
mg/kg
significantly
reduced
Racine's
scale
duration
seizures,
increased
onset
time
seizure.
Moreover,
caused
significant
reductions
elevated
IL-lβ
TNF-α,
increase
decreased
level
CB1
receptor
compared
group.
In
other
word,
reverted
terms
neuroinflammation
receptor.
Based
obtained
results,
not
able
restore
declined
CB2
or
receptors.
Conclusion:
Our
found
rat
model
lithium-pilocarpine
with
probable
reducing
IL-1β
TNF-α
markers
independent
