bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 19, 2024
ABSTRACT
Social
behaviors
are
critical
for
survival
and
fitness
of
a
species,
maladaptive
social
frequently
associated
with
neurodevelopmental
psychiatric
disorders.
As
such,
the
neural
circuits
cellular
mechanisms
driving
inform
processes
contributing
to
both
health
disease.
In
particular,
nucleus
accumbens
(NAc)
is
key
hub
integration
non-social
information
required
successful
interactions
reward
motivated
behaviors.
While
astrocytes
within
NAc
have
recognized
role
in
modulating
activity,
their
influence
over
behavior
yet
undefined.
To
address
this
question,
we
manipulated
astrocyte
signaling
determined
effects
on
interactions.
core
bidirectionally
influenced
rats;
agonism
astrocyte-specific
hM3D(Gq)
DREADD
receptors
increased
interaction
time
test
preference
3-chamber
test.
Conversely,
decreasing
intracellular
calcium
viral
expression
hPMCA
reduced
these
tests.
These
results
suggest
that
actively
participate
regulation
highlight
putative
disorders
characterized
by
dysfunction.
Journal of Neuropathology & Experimental Neurology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 2, 2025
Abstract
Spinal
cord
injury
(SCI)
constitutes
a
profound
central
nervous
system
disorder
characterized
by
significant
neurological
dysfunction
and
sensory
loss
below
the
site.
SCI
elicits
multifaceted
cellular
response
in
which
proliferation
of
reactive
astrocytes
ensuing
diversity
their
functions
phenotypes
play
pivotal
roles
within
microenvironment,
especially
during
secondary
phases
condition.
This
review
explores
activation
heterogeneity
following
SCI.
It
underscores
necessity
delineating
among
astrocyte
subpopulations
throughout
phase
Developing
therapeutic
strategies
that
capitalize
on
beneficial
properties
certain
while
mitigating
adverse
effects
others
could
have
implications
for
future
clinical
management
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Май 14, 2025
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
disorder
characterized
by
cognitive
decline,
amyloid-beta
(Aβ)
aggregation,
tau
pathology,
and
chronic
neuroinflammation.
Among
these,
neuroinflammation
plays
crucial
role
in
exacerbating
progression,
making
it
an
attractive
therapeutic
target.
However,
the
presence
of
blood-brain
barrier
(BBB)
significantly
limits
effective
delivery
agents
to
brain,
necessitating
novel
drug
strategies.
Nanocarrier-based
systems
have
emerged
as
promising
solution
these
challenges,
offering
targeted
transport,
enhanced
BBB
penetration,
improved
bioavailability
while
minimizing
systemic
toxicity.
This
review
explores
current
advancements
nanocarrier-mediated
for
AD,
focusing
on
mechanisms
neuroinflammation,
nanocarriers
overcoming
BBB,
their
ability
modulate
inflammatory
pathways.
Furthermore,
discusses
preclinical
validation
strategies
key
including
safety
concerns,
large-scale
production
limitations,
regulatory
hurdles
that
must
be
addressed
enable
clinical
translation.
Future
perspectives
emphasize
integration
nanotechnology
with
precision
medicine,
gene
therapy,
artificial
intelligence
optimize
nanocarrier
design
individualized
AD
treatment.
By
obstacles,
hold
potential
revolutionize
approaches
other
diseases.
Journal of Neurochemistry,
Год журнала:
2025,
Номер
169(5)
Опубликована: Май 1, 2025
ABSTRACT
Obsessive‐compulsive
disorder
(OCD)
has
long
been
conceptualized
as
a
neuron‐centric
of
cortico‐striato‐thalamo‐cortical
(CSTC)
circuit
dysregulation.
However,
growing
body
evidence
is
now
reframing
this
narrative,
placing
astrocytes—once
relegated
to
passive
support
roles—at
the
center
OCD
pathophysiology.
Astrocytes
are
critical
regulators
glutamate
and
GABA
homeostasis,
calcium
signaling,
synaptic
plasticity,
all
which
disrupted
in
OCD.
Recent
high‐resolution
molecular
proteomic
studies
reveal
that
specific
astrocyte
subpopulations,
including
Crym
‐positive
astrocytes,
directly
shape
excitatory/inhibitory
balance
control
perseverative
behaviors
by
modulating
presynaptic
inputs
from
orbitofrontal
cortex.
Disruptions
astrocytic
neurotransmitter
clearance
dopamine
metabolism
amplify
CSTC
hyperactivity
reinforce
compulsions.
This
review
reframes
neuro‐glial
dysfunctions,
proposing
targeting
metabolism,
structural
plasticity
may
unlock
transformative
therapeutic
strategies.
By
integrating
human
animal
data,
we
advocate
for
glial‐centric
model
not
only
enhances
mechanistic
understanding
but
also
opens
new
frontiers
precision
treatment.
image
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 21, 2024
Summary
Rodent
drug
self-administration
leads
to
compromised
ability
of
astrocytes
maintain
glutamate
homeostasis
within
the
brain’s
reward
circuitry,
as
well
reductions
in
surface
area,
volume,
and
synaptic
colocalization
astrocyte
membranes.
However,
mechanisms
driving
responses
cocaine
are
unknown.
Here,
we
report
that
long-access
followed
by
prolonged
home
cage
abstinence
results
decreased
branching
complexity
nucleus
accumbens
astrocytes,
characterized
loss
peripheral
processes.
Using
a
combination
confocal
fluorescence
microcopy
immuno-gold
electron
microscopy,
show
alterations
structural
features
driven
microglia
phagocytosis,
labeled
membranes
found
phagolysosomes.
Inhibition
complement
C3-mediated
phagocytosis
using
neutrophil
inhibitory
peptide
(NIF)
rescued
structure
seeking
behavior
following
abstinence.
Collectively,
these
provide
evidence
for
pruning
across
which
mediates
craving.
