Aging and Disease,
Год журнала:
2024,
Номер
unknown, С. 0 - 0
Опубликована: Янв. 1, 2024
Depression
represents
a
prevalent
and
enduring
mental
disorder
of
significant
concern
within
the
clinical
domain.
Extensive
research
indicates
that
depression
is
very
complex,
with
many
interconnected
pathways
involved.
Most
related
to
focuses
on
monoamines,
neurotrophic
factors,
hypothalamic-pituitary-adrenal
axis,
tryptophan
metabolism,
energy
mitochondrial
function,
gut-brain
glial
cell-mediated
inflammation,
myelination,
homeostasis,
brain
neural
networks.
However,
recently,
Ketamine,
an
ionotropic
N-methyl-D-aspartate
(NMDA)
receptor
antagonist,
has
been
discovered
have
rapid
antidepressant
effects
in
patients,
leading
novel
successful
treatment
approaches
for
mood
disorders.
This
review
aims
summarize
latest
findings
insights
into
various
signaling
systems
observed
patients
animal
models,
providing
more
comprehensive
view
neurobiology
anxious-depressive-like
behavior.
Specifically,
it
highlights
key
mechanisms
ketamine
as
rapid-acting
antidepressant,
aiming
enhance
neuropsychiatric
Moreover,
we
discuss
potential
prophylactic
or
therapeutic
intervention
stress-related
psychiatric
Post-stroke
depression
is
a
common
complication
that
imposes
significant
burdens
and
challenges
on
patients.
The
occurrence
of
often
associated
with
frontal
lobe
hemorrhage,
however,
current
understanding
the
underlying
mechanisms
remains
limited.
Here,
pathogenic
circuitry
connectivity,
electrophysiological
alterations,
molecular
characteristics
are
investigated
related
to
in
adult
male
mice
following
unilateral
injection
blood
medial
prefrontal
cortex
(mPFC).
It
demonstrated
specific
neurological
hematoma
model
mPFC,
ventral
tegmental
area
(VTA)
shows
higher
percentage
connectivity
disruption
compared
lateral
habenula
(LHb)
striatum
(STR).
Additionally,
long-range
projections
originating
from
demonstrate
damage
percentages
within
connections
between
each
region
mPFC.
mPFC
neurons
reveal
reduced
neuronal
excitability
altered
synaptic
communication.
Furthermore,
transcriptomic
analysis
identifies
involvement
Janus
Kinase-Signal
Transducer
Activator
Transcription
(JAK-STAT)
signaling
pathway,
targeting
JAK-STAT
pathway
significantly
alleviates
severity
depressive
symptoms.
These
findings
improve
post-hemorrhagic
may
guide
development
efficient
treatments.
Behavioural Neurology,
Год журнала:
2025,
Номер
2025(1)
Опубликована: Янв. 1, 2025
Astrocytes
are
the
primary
cell
type
in
central
nervous
system,
responsible
for
maintaining
stability
of
brain’s
internal
environment
and
supporting
neuronal
functions.
Researches
have
demonstrated
close
relationship
between
astrocytes
pathophysiology
etiology
major
depressive
disorder.
However,
regulatory
mechanisms
during
depression
remain
unclear.
The
aim
this
study
is
to
examine
alterations
calcium
signaling
dorsal
raphe
nucleus
(DRN),
neurons
both
DRN
medial
prefrontal
cortex
(mPFC),
alteration
depressive‐like
behaviors
by
activation
using
chemogenetics
chronic
social
defeat
stress
(CSDS)
mice.
results
showed
that
intensity
was
decreased
frequency
lower
after
CSDS.
increased
including
CaMKII
α
mPFC
(via
neural
circuit
mPFC).
were
improved
activating
CSDS
Our
suggest
an
important
role
findings
offer
new
insights
treatment
depression.
Translational Psychiatry,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 14, 2025
A
longed
lack
of
control
over
harmful
stimuli
can
lead
to
learned
helplessness
(LH),
a
significant
factor
in
depression.
However,
the
cellular
and
molecular
mechanisms
underlying
LH,
eventually
behavioral
despair,
remain
largely
unknown.
The
deleted
colorectal
cancer
(dcc)
gene
is
associated
with
risk
therapeutic
potential
regulation
mechanism
DCC
despair
are
still
uncertain.
In
this
study,
we
showed
that
depressive
stimulators,
including
lipopolysaccharide,
unpredictable
chronic
mild
stress,
triggered
an
elevation
expression
medial
prefrontal
cortex
(mPFC).
Additionally,
elevated
mPFC
was
crucial
inducing
as
evidenced
by
induction
normal
mice
exacerbation
LH
upon
overexpression.
By
contrast,
neutralizing
activity
ameliorated
LH-induced
despair.
Importantly,
elucidated
pathological
attributable
excessive
excitation
CaMKII+
neurons
manner
dependent
on
calpain-mediated
degradation
SCOP
aberrant
phosphorylation
ERK
signaling
pathway.
addition,
increase
led
decreased
excitability
threshold
mPFC,
which
supported
observation
ligand
netrin
1
increased
frequency
action
firing
spontaneous
excitatory
postsynaptic
currents
neurons.
conclusion,
our
data
indicate
triggers
activation
calpain-SCOP/ERK
promote
expression,
represents
target
for
treatment
male
mice.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 14, 2025
Astrocytes
are
closely
linked
to
depression,
and
the
prefrontal
cortex
(PFC)
is
an
important
brain
region
involved
in
major
depressive
disorder
(MDD).
However,
underlying
mechanism
by
which
astrocytes
within
PFC
contribute
MDD
remains
unclear.
Using
single-nucleus
RNA
sequencing
analyses,
we
show
a
significant
reduction
attenuated
pleiotrophin-protein
tyrosine
phosphatase
receptor
type
Z1
(PTN-PTPRZ1)
signaling
astrocyte-to-excitatory
neuron
communication
of
male
patients.
We
find
reduced
PTN
dorsomedial
mice
with
depression
induced
chronic
restraint
social
defeat
stress.
Knockdown
astrocytic
induces
depression-related
responses,
reversed
exogenous
supplementation
or
overexpression
PTN.
The
antidepressant
effects
exerted
require
interaction
PTPRZ1
excitatory
neurons,
PTN-PTPRZ1
activates
AKT
pathway
regulate
responses.
Our
findings
indicate
PTN-PTPRZ1-AKT
may
be
potential
therapeutic
target
for
MDD.
but
mechanisms
remain
Here,
authors
that
pleiotrophin
contributes
depression-like
phenotype
mice.
Journal of Neurochemistry,
Год журнала:
2025,
Номер
169(4)
Опубликована: Апрель 1, 2025
The
inositol
1,4,5-triphosphate
receptor
type
2
(IP3R2)
plays
a
critical
role
in
intracellular
calcium
(Ca2+)
signaling,
particularly
astrocytes,
where
it
mediates
Ca2+
release
from
the
endoplasmic
reticulum.
This
mechanism
is
vital
for
astrocytic
modulation
of
neuronal
networks,
impacting
synaptic
transmission
and
broader
neural
circuit
functions.
IP3R2
knockout
(IP3R2KO)
mouse
model
has
been
instrumental
unraveling
nuances
somatic
dynamics
their
implications
brain
function.
Despite
early
findings
suggesting
no
significant
behavioral
or
changes
IP3R2KO
mice,
further
research
highlights
model's
benefit
exploring
cognitive,
emotional,
neurodevelopmental
processes.
mice
revealed
key
insights
into
signaling
diversity,
encompassing
bulk
events
localized
microdomain
responses,
which
exhibit
temporal
spatial
variability.
These
animals
retain
alternative
mechanisms,
likely
explaining
absence
severe
phenotypes
some
contexts.
Nevertheless,
impairments
long-term
memory
retention,
working
memory,
fear
alongside
age-related
preservation
linking
to
higher-order
cognitive
Additionally,
studies
suggest
connection
between
pathways
depression-like
behaviors,
with
alterations
Brain-Derived
Neurotrophic
Factor
(BDNF)
levels
GABAergic
highlighting
its
relevance
psychiatric
conditions.
limitations,
such
as
residual
activity
inconsistent
findings,
remains
valuable
tool
studying
contributions
plasticity
underscores
importance
integrating,
rather
than
dismissing,
development
new
methodologies
dynamics.
use
this
will
continue
elucidate
complex
interplay
astrocytes
circuits,
fostering
advances
understanding
signaling's
health
disease.
