Nature Communications,
Journal Year:
2019,
Volume and Issue:
10(1)
Published: March 29, 2019
Abstract
The
ventral
tegmental
area
(VTA)
is
a
heterogeneous
midbrain
structure,
containing
neurons
and
astrocytes,
that
coordinates
behaviors
by
integrating
activity
from
numerous
afferents.
Within
neuron-astrocyte
networks,
astrocytes
control
signals
distinct
afferents
in
circuit-specific
manner,
but
whether
this
capacity
scales
up
to
drive
motivated
behavior
has
been
undetermined.
Using
genetic
optical
dissection
strategies
we
report
VTA
tune
glutamatergic
signaling
selectively
on
local
inhibitory
functional
circuit
for
learned
avoidance.
In
circuit,
facilitate
excitation
of
GABA
increase
inhibition
dopamine
neurons,
eliciting
real-time
avoidance
sufficient
impede
expression
preference
reward.
Loss
one
glutamate
transporter
(GLT-1)
blocks
these
spares
Thus,
regulate
opposes
approach
behavior.
Nature Medicine,
Journal Year:
2023,
Volume and Issue:
29(11), P. 2866 - 2884
Published: Oct. 9, 2023
Abstract
Huntington’s
disease
(HD)
is
a
devastating
monogenic
neurodegenerative
characterized
by
early,
selective
pathology
in
the
basal
ganglia
despite
ubiquitous
expression
of
mutant
huntingtin.
The
molecular
mechanisms
underlying
this
region-specific
neuronal
degeneration
and
how
these
relate
to
development
early
cognitive
phenotypes
are
poorly
understood.
Here
we
show
that
there
loss
synaptic
connections
between
cortex
striatum
postmortem
tissue
from
patients
with
HD
associated
increased
activation
localization
complement
proteins,
innate
immune
molecules,
elements.
We
also
found
levels
secreted
molecules
elevated
cerebrospinal
fluid
premanifest
correlate
established
measures
burden.
In
preclinical
genetic
models
HD,
proteins
mediate
elimination
corticostriatal
synapses
at
an
stage
pathogenesis,
marking
them
for
removal
microglia,
brain’s
resident
macrophage
population.
This
process
requires
huntingtin
be
expressed
both
cortical
striatal
neurons.
Inhibition
complement-dependent
mechanism
through
administration
therapeutically
relevant
C1q
function-blocking
antibody
or
ablation
receptor
on
microglia
prevented
synapse
loss,
excitatory
input
rescued
visual
discrimination
learning
flexibility
deficits
models.
Together,
our
findings
implicate
cascade
selective,
presymptomatic
HD;
they
provide
new
data
support
as
therapeutic
target
intervention.
Nature,
Journal Year:
2023,
Volume and Issue:
616(7958), P. 764 - 773
Published: April 12, 2023
Astrocytes
and
neurons
extensively
interact
in
the
brain.
Identifying
astrocyte
neuron
proteomes
is
essential
for
elucidating
protein
networks
that
dictate
their
respective
contributions
to
physiology
disease.
Here
we
used
cell-specific
subcompartment-specific
proximity-dependent
biotinylation1
study
of
striatal
astrocytes
vivo.
We
evaluated
cytosolic
plasma
membrane
compartments
discover
how
these
cells
differ
at
level
signalling
machinery.
also
assessed
subcellular
astrocytes,
including
end
feet
fine
processes,
reveal
subproteomes
molecular
basis
homeostatic
functions.
Notably,
SAPAP3
(encoded
by
Dlgap3),
which
associated
with
obsessive-compulsive
disorder
(OCD)
repetitive
behaviours2-8,
was
detected
high
levels
enriched
within
specific
subcompartments
where
it
regulated
actin
cytoskeleton
organization.
Furthermore,
genetic
rescue
experiments
combined
behavioural
analyses
assessments
a
mouse
model
OCD4
lacking
revealed
distinct
astrocytic
neuronal
anxiety-related
OCD-like
phenotypes.
Our
data
define
major
pathways.
Moreover,
they
vary
between
physiological
both
mechanisms
contribute
OCD
phenotypes
mice.
indicate
therapeutic
strategies
target
may
be
useful
explore
potentially
other
brain
disorders.
Trends in Cell Biology,
Journal Year:
2023,
Volume and Issue:
34(7), P. 547 - 565
Published: Oct. 26, 2023
Astrocytes
are
predominant
glial
cells
that
tile
the
central
nervous
system
(CNS).
A
cardinal
feature
of
astrocytes
is
their
complex
and
visually
enchanting
morphology,
referred
to
as
bushy,
spongy,
star-like.
precept
this
review
such
morphological
shapes
evolved
allow
contact
signal
with
diverse
at
a
range
distances
in
order
sample,
regulate,
contribute
extracellular
milieu,
thus
participate
widely
cell–cell
signaling
during
physiology
disease.
The
recent
use
improved
imaging
methods
cell-specific
molecular
evaluations
has
revealed
new
information
on
structural
organization
underpinnings
astrocyte
mechanisms
morphogenesis,
contributions
disease
states
reduced
morphology.
These
insights
have
reignited
interest
complexity
cornerstone
fundamental
biology
critical
substrate
for
multicellular
spatial
physiological
interactions
CNS.
Cell Death and Disease,
Journal Year:
2023,
Volume and Issue:
14(5)
Published: May 29, 2023
Abstract
Astrocyte
atrophy
is
the
main
histopathological
hallmark
of
major
depressive
disorder
(MDD)
in
humans
and
animal
models
depression.
Here
we
show
that
electroacupuncture
prevents
astrocyte
prefrontal
cortex
alleviates
depressive-like
behaviour
mice
subjected
to
chronic
unpredictable
mild
stress
(CUMS).
Treatment
with
CUMS
induced
phenotypes
as
confirmed
by
sucrose
preference
test,
tail
suspension
forced
swimming
test.
These
behavioural
changes
were
paralleled
morphological
astrocytes
cortex,
revealed
analysis
3D
reconstructions
confocal
Z-stack
images
mCherry
expressing
astrocytes.
This
was
accompanied
a
decrease
expression
cytoskeletal
linker
Ezrin,
associated
formation
astrocytic
leaflets,
which
form
astroglial
synaptic
cradle.
Electroacupuncture
at
acupoint
ST36,
well
treatment
anti-depressant
fluoxetine,
prevented
behaviours,
atrophy,
down-regulation
ezrin.
In
conclusion,
our
data
further
strengthen
notion
primary
role
depression
reveal
cellular
target
for
disorders.
Nature,
Journal Year:
2024,
Volume and Issue:
627(8003), P. 358 - 366
Published: Feb. 28, 2024
Abstract
Astrocytes
are
heterogeneous
glial
cells
of
the
central
nervous
system
1–3
.
However,
physiological
relevance
astrocyte
diversity
for
neural
circuits
and
behaviour
remains
unclear.
Here
we
show
that
a
specific
population
astrocytes
in
striatum
expresses
μ-crystallin
(encoded
by
Crym
mice
CRYM
humans)
is
associated
with
several
human
diseases,
including
neuropsychiatric
disorders
4–7
In
adult
mice,
reducing
levels
striatal
through
CRISPR–Cas9-mediated
knockout
resulted
perseverative
behaviours,
increased
fast
synaptic
excitation
medium
spiny
neurons
dysfunctional
excitatory–inhibitory
balance.
Increased
perseveration
stemmed
from
loss
astrocyte-gated
control
neurotransmitter
release
presynaptic
terminals
orbitofrontal
cortex–striatum
projections.
We
found
could
be
remedied
using
inhibitory
chemogenetics
8
,
this
treatment
also
corrected
deficits.
Together,
our
findings
reveal
converging
molecular,
synaptic,
circuit
behavioural
mechanisms
which
molecularly
defined
allocated
gates
phenotypes
accompany
9–12
Our
data
-positive
have
key
biological
functions
within
system,
uncover
astrocyte–neuron
interaction
targeted
treatments
perseveration.
