Frontiers in Psychiatry,
Год журнала:
2023,
Номер
14
Опубликована: Май 11, 2023
In
a
subset
of
patients,
chronic
exposure
to
stress
is
an
etiological
risk
factor
for
neuroinflammation
and
depression.
Neuroinflammation
affects
up
27%
patients
with
MDD
associated
more
severe,
chronic,
treatment-resistant
trajectory.
Inflammation
not
unique
depression
has
transdiagnostic
effects
suggesting
shared
underlying
psychopathologies
metabolic
disorders.
Research
supports
association
but
necessarily
causation
Putative
mechanisms
link
dysregulation
the
HPA
axis
immune
cell
glucocorticoid
resistance
resulting
in
hyperactivation
peripheral
system.
The
extracellular
release
DAMPs
DAMP-PRR
signaling
creates
feed
forward
loop
that
accelerates
central
inflammation.
Higher
plasma
levels
inflammatory
cytokines,
most
consistently
interleukin
IL-1β,
IL-6,
TNF-α,
are
correlated
greater
depressive
symptomatology.
Cytokines
sensitize
axis,
disrupt
negative
feedback
loop,
further
propagate
reactions.
Peripheral
inflammation
exacerbates
(neuroinflammation)
through
several
including
disruption
blood-brain
barrier,
cellular
trafficking,
activation
glial
cells.
Activated
cells
chemokines,
reactive
oxygen
nitrogen
species
into
extra-synaptic
space
dysregulating
neurotransmitter
systems,
imbalancing
excitatory
inhibitory
ratio,
disrupting
neural
circuitry
plasticity
adaptation.
particular,
microglial
toxicity
plays
role
pathophysiology
neuroinflammation.
Magnetic
resonance
imaging
(MRI)
studies
show
reduced
hippocampal
volumes.
Neural
dysfunction
such
as
hypoactivation
between
ventral
striatum
ventromedial
prefrontal
cortex
underlies
melancholic
phenotype
Chronic
administration
monoamine-based
antidepressants
counters
response,
delayed
therapeutic
onset.
Therapeutics
targeting
mediated
immunity,
generalized
specific
pathways,
nitro-oxidative
have
enormous
potential
advance
treatment
landscape.
Future
clinical
trials
will
need
include
system
perturbations
biomarker
outcome
measures
facilitate
novel
antidepressant
development.
this
overview,
we
explore
correlates
elucidate
pathomechanisms
development
biomarkers
therapeutics.
Journal of Clinical Medicine,
Год журнала:
2024,
Номер
13(6), С. 1727 - 1727
Опубликована: Март 17, 2024
Major
Depressive
Disorder
(MDD)
is
one
of
the
most
disabling
diseases
in
world.
MDD
traditionally
diagnosed
based
on
a
patient’s
symptoms,
which
can
lead
to
misdiagnosis.
Although
pathogenic
mechanisms
are
unknown,
several
studies
have
identified
mitochondrial
dysfunction
as
central
factor
onset
and
progression
MDD.
In
context
MDD,
alterations
metabolism
imbalances
energy
production
oxidative
stress,
contributing
disorder´s
underlying
pathophysiological
mechanisms.
Consequently,
identification
key
biomarker
for
early
accurate
diagnosis
represents
significant
challenge.
Faced
with
limits
traditional
treatments
antidepressants,
new
pharmacological
therapeutic
targets
being
investigated
such
ketamine/esketamine,
psychedelics,
or
anti-inflammatories.
All
these
drugs
show
potential
antidepressant
effects
due
their
speed
action
ability
modulate
neuroplasticity
and/or
motor
processing.
parallel,
non-pharmacological
studied,
like
Transcranial
Magnetic
Stimulation
(TMS)
Deep
Brain
(DBS),
recognized
neuronal
activity
offer
treatment
alternatives.
As
cellular
directly
related
respiration,
aim
this
review
examining
link
between
assessing
how
biomarkers
could
provide
more
objective
precise
diagnostic
tool,
exploring
other
addition
specific
focus
emerging
targets.
Finally,
detailed
analysis
strengths,
weaknesses,
opportunities,
threats
approaches
was
carried
out,
highlighting
challenges
that
must
be
addressed.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(8), С. 6888 - 6888
Опубликована: Апрель 7, 2023
Major
depressive
disorder
is
one
of
the
most
common
mental
illnesses
that
highly
impairs
quality
life.
Pharmacological
interventions
are
mainly
focused
on
altered
monoamine
neurotransmission,
which
considered
primary
event
underlying
disease's
etiology.
However,
many
other
neuropathological
mechanisms
contribute
to
progression
and
clinical
symptoms
have
been
identified.
These
include
oxidative
stress,
neuroinflammation,
hippocampal
atrophy,
reduced
synaptic
plasticity
neurogenesis,
depletion
neurotrophic
factors,
dysfunction
hypothalamic-pituitary-adrenal
(HPA)
axis.
Current
therapeutic
options
often
unsatisfactory
associated
with
adverse
effects.
This
review
highlights
relevant
findings
concerning
role
flavonols,
a
ubiquitous
class
flavonoids
in
human
diet,
as
potential
antidepressant
agents.
In
general,
flavonols
be
both
an
effective
safe
option
management
depression,
largely
based
their
prominent
antioxidative
anti-inflammatory
Moreover,
preclinical
studies
provided
evidence
they
capable
restoring
neuroendocrine
control
HPA
axis,
promoting
alleviating
depressive-like
behavior.
Although
these
promising,
still
far
from
being
implemented
practice.
Hence,
further
needed
more
comprehensively
evaluate
respect
improvement
signs
depression.
CNS Neuroscience & Therapeutics,
Год журнала:
2023,
Номер
30(4)
Опубликована: Ноя. 12, 2023
Abstract
Depression
is
a
mood
disorder
characterized
by
abnormal
thoughts.
The
pathophysiology
of
depression
related
to
the
deficiency
serotonin
(5HT),
which
derived
from
tryptophan
(Trp).
Mitochondrial
dysfunction,
oxidative
stress,
and
neuroinflammation
are
involved
in
pathogenesis
depression.
Notably,
renin–angiotensin
system
(RAS)
depression,
different
findings
revealed
that
angiotensin‐converting
enzyme
inhibitors
(ACEIs)
angiotensin
receptor
blockers
(ARBs)
may
be
effective
However,
underlying
mechanism
for
role
dysregulated
brain
RAS‐induced
remains
speculative.
Therefore,
this
review
aimed
revise
conceivable
ACEIs
ARBs
how
these
agents
ameliorate
Dysregulation
RAS
triggers
development
progression
through
reduction
5HT
expression
brain‐derived
neurotrophic
factor
(BDNF)
induction
mitochondrial
neuroinflammation.
inhibition
central
classical
ARBS
activation
non‐classical
prevent
regulating
5HT,
BDNF,
Biomolecules,
Год журнала:
2025,
Номер
15(4), С. 502 - 502
Опубликована: Март 30, 2025
Depression
is
a
multifactorial
psychiatric
condition
with
complex
pathophysiology,
increasingly
linked
to
neuroinflammatory
processes.
The
present
review
explores
the
role
of
neuroinflammation
in
depression,
focusing
on
glial
cell
activation,
cytokine
signaling,
blood-brain
barrier
dysfunction,
and
disruptions
neurotransmitter
systems.
article
highlights
how
inflammatory
mediators
influence
brain
regions
implicated
mood
regulation,
such
as
hippocampus,
amygdala,
prefrontal
cortex.
further
discusses
involvement
hypothalamic-pituitary-adrenal
(HPA)
axis,
oxidative
stress,
kynurenine
pathway,
providing
mechanistic
insights
into
chronic
inflammation
may
underlie
emotional
cognitive
symptoms
depression.
bidirectional
relationship
between
depressive
emphasized,
along
peripheral
immune
responses
systemic
stress.
By
integrating
molecular,
cellular,
neuroendocrine
perspectives,
this
supports
growing
field
immunopsychiatry
lays
foundation
for
novel
diagnostic
biomarkers
anti-inflammatory
treatment
approaches
Further
research
holds
promise
developing
more
effective
personalized
interventions
individuals
suffering
from
Frontiers in Bioscience-Landmark,
Год журнала:
2023,
Номер
28(11), С. 311 - 311
Опубликована: Ноя. 28, 2023
Background:
Breast
cancer-related
depression
(BCRD)
is
strongly
associated
with
BC
and
increases
recurrence
mortality.
This
study
investigated
the
role
of
kaempferol
in
pathogenesis
BCRD
its
underlying
mechanism.
Methods:
4T1
mouse
cells
were
treated
corticosterone
(Cort)
vitro
to
develop
a
neuronal
injury
model,
model
was
established
by
injecting
Cort.
The
effects
on
models
measured
behavioral
tests,
Cell
Counting
Kit-8
assay,
wound
healing
colony
formation
Western
blot
analysis,
quantitative
real-time
PCR,
hematoxylin
eosin
staining,
enzyme-linked
immunosorbent
immunofluorescence.
transfected
cyclo-oxygenase-2
(COX-2)
overexpression
plasmid
COX-2/prostaglandin
E2
(PGE2)
axis
anti-BCRD
activity
kaempferol.
connection
between
COX-2
analyzed
molecular
docking.
Results:
Kaempferol
reduced
viability,
migration,
clones
inhibited
growth
depression-like
behavior
mice.
alleviated
inflammation
BCRD,
decreased
interleukin
1
beta
(IL-1β)
IL-6
levels,
increased
transforming
factor
(TGF-β1)
IL-10
levels.
In
addition,
elevated
levels
serotonin,
dopamine,
norepinephrine
amount
5-Bromo-2′-deoxyuridine/neuronal
nuclei-positive
cells.
downregulated
PGE2,
could
dock
protein
structure
COX-2.
Overexpression
upregulated
IL-1β
TGF-β1
expression.
reversed
protective
Conclusion:
exerted
effects,
at
least
part
inhibiting
COX-2/PGE2
pathway,
which
regulates
neuroinflammation,
neurotransmitter
imbalance,
defective
neurogenesis.
Therefore,
may
be
promising
candidate
active
ingredient
for
treating
BCRD.
Nutrients,
Год журнала:
2024,
Номер
16(8), С. 1167 - 1167
Опубликована: Апрель 14, 2024
Polygonati
Rhizoma
(PR)
has
certain
neuroprotective
effects
as
a
homology
of
medicine
and
food.
In
this
study,
systematic
pharmacology,
molecular
docking,
in
vitro
experiments
were
integrated
to
verify
the
antidepressant
active
ingredients
PR
their
mechanisms.
A
total
seven
compounds
found
be
associated
with
45
targets
depression.
Preliminarily,
DFV
docking
cyclooxygenase
2
(COX2)
showed
good
affinity.
vitro,
inhibited
lipopolysaccharide
(LPS)-induced
inflammation
BV-2
cells,
reversed
amoeba-like
morphological
changes,
increased
mitochondrial
membrane
potential.
malondialdehyde
(MDA)
overexpression
superoxide
dismutase
(SOD)
expression
inhibition
LPS-induced
cells
decreased
interleukin-1β
(IL-1β),
tumor
necrosis
factor-α
(TNF-α),
IL-6
mRNA
levels
dose-dependent
manner.
both
protein
COX2
induced
by
LPS,
activation
NACHT,
LRR,
PYD
domains-containing
3
(NLRP3)
caspase1
was
suppressed,
thus
exerting
an
effect.
This
study
proves
that
may
important
component
basis
for
play
role.
Frontiers in Psychiatry,
Год журнала:
2024,
Номер
15
Опубликована: Авг. 23, 2024
Background
The
incidence
rate
of
adolescent
depression
and
anxiety
has
been
increasing
since
the
outbreak
COVID-19,
which
there
are
no
effective
therapeutic
drugs
available.
Si-ni
San
is
commonly
used
in
traditional
Chinese
medicine
for
treatment
depression-like
as
well
anxiety-like
behavior,
but
its
mechanism
treating
combined
with
during
adolescence
not
yet
clear.
Methods
Network
pharmacology
was
to
explore
potential
drug
molecules
related
targets,
molecular
docking
dynamics
(MD)
simulation
were
evaluate
interaction
between
a
model
rats
following
behavioral
tests
biology
verify
results
from
network
docking.
Results
As
result,
256
active
ingredients
1128
targets
screened
out.
Among
them,
quercetin,
Luteolin,
kaempferol,
7-Methoxy-2-methyl
isoflavone,
formononetin
showed
be
most
ingredients;
while
STAT3,
IL6,
TNF,
AKT1,
TP53,
IL1B,
MAPK3,
VEGFA,
CASP3,
MMP9
targets.
AGE-RAGE
signaling
pathway
diabetic
complications,
IL-17
pathway,
HIF-1
PI3K-Akt
TNF
involved
anti-inflammation
processes,
probable
pathways
regulated
by
San.
Molecular
MD
compounds
inflammation-associated
revealed
good
binding
abilities
nobiletin
PTGS2
PPARγ.
In
experiment
rats,
markedly
suppressed
early
maternal
separation
(MS)
chronic
unpredictable
mild
stress
(CUMS)-induced
anxiety.
qPCR
further
indicated
that
oxidative
inflammatory
response.
Conclusion
This
study
demonstrates
anxiety-
behavior
induced
MS
CUMS
can
ameliorated
improved
inflammation
hippocampus
via
targeting
Nrf2
helping
reveal
