Urolithin A alleviates schizophrenic-like behaviors and cognitive impairment in rats through modulation of neuroinflammation, neurogenesis, and synaptic plasticity
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 26, 2025
Cognitive
impairment
in
schizophrenia
occurs
the
early
stages
of
disease
and
is
closely
associated
with
prognosis.
Alleviation
cognitive
faces
major
challenges
owing
to
lack
preventive
therapeutic
drugs
that
are
novel
effective.
Urolithin
A
(UA)
a
gut
microbial
metabolite
ellagic
acid
has
demonstrated
neuroprotective
effects
multiple
neurological
models.
Nonetheless,
neuromodulatory
role
UA
yet
be
elucidated.
Wistar
rat
pups
were
separated
from
their
mothers
for
24
h
on
postnatal
days
(PNDs)
9–10
establish
an
early-life
stress
model.
The
pretreated
at
different
administration
times
(2,
4,
6
weeks)
doses
(50,
100,
150
mg/kg)
adolescence
(PND29).
Behavioral
tests
performed
after
end
administration.
Subsequently,
hippocampal
samples
collected
histopathological
molecular
evaluations.
Male
offspring
rats
subjected
maternal
separation
exhibited
increased
sensitivity
prepulse
inhibition
impairment,
accompanied
by
severe
neuroinflammation
impaired
neurogenesis.
However,
attenuated
separation-induced
deficits
impairments
restored
neurogenesis
dose-dependent
manner.
Furthermore,
pretreatment
preserved
dendritic
spine
density,
synapses,
presynaptic
vesicles.
In
addition,
it
exerted
anti-inflammatory
inhibiting
microglial
activation
expression
proinflammatory
cytokines
tumor
necrosis
factor-α,
interleukin-6,
interleukin-1β.
Potential
mechanisms
included
upregulation
brain-derived
neurotrophic
factor
protein
extracellular
signal-regulated
kinase
signaling
pathway.
This
study
first
preclinical
evaluation
schizophrenia.
findings
suggest
changes
function
linked
driven
interaction
among
neuroinflammation,
neurogenesis,
synaptic
plasticity
potential
reverse
these
processes.
These
observations
provide
evidence
future
clinical
trials
as
dietary
supplement
preventing
Язык: Английский
Indomethacin Partially Alleviates Depressive‐Like Behaviors in Maternally Separated Mice: Targeting Neuroinflammatory Response in the Hippocampus
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2025,
Номер
39(5)
Опубликована: Май 1, 2025
ABSTRACT
Experiencing
early‐life
stress
(ELS)
plays
a
fundamental
role
in
the
development
of
mood
disorders
like
depression
adulthood.
Neuro‐immune
response
brain
is
coupled
with
depressive‐like
behaviors
following
maternal
separation
(MS)
stress.
Indomethacin
(IND)
nonsteroidal
anti‐inflammatory
drug.
This
study
aimed
to
assess
antidepressant‐like
effect
IND
mouse
model
MS
stress,
focusing
on
its
potential
neuro‐inflammatory
hippocampus.
To
do
this,
male
NMRI
mice
were
treated
at
doses
5,
10,
and
20
mg/kg,
saline
(10
mL/kg)
or
fluoxetine
(30
mg/kg).
Drugs
injected
intraperitoneally
for
7
days.
Behavioral
tests
including
forced
swimming
test,
splash
open
field
test
performed.
Quantitative
reverse
transcription‐PCR
was
used
evaluation
gene
expression
inflammatory
mediators
iNOS
,
TLR4
NLRP3
TNF‐α
IL‐1β
Results
showed
that
provoked
behavior
as
observed
by
decrease
grooming
activity
time
an
increase
immobility
test.
Depressive‐like
neuroinflammation
attenuated
well
decreased
neuroinflammation‐related
hippocampus
mice.
In
conclusion,
results
IND,
least
part,
via
alleviation
hippocampus,
exerted
effects
Язык: Английский