Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Март 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.
Annual Review of Neuroscience,
Год журнала:
2019,
Номер
42(1), С. 187 - 207
Опубликована: Июль 8, 2019
Astrocytes
are
morphologically
complex,
ubiquitous
cells
that
viewed
as
a
homogeneous
population
tiling
the
entire
central
nervous
system
(CNS).
However,
this
view
has
been
challenged
in
last
few
years
with
availability
of
RNA
sequencing,
immunohistochemistry,
electron
microscopy,
morphological
reconstruction,
and
imaging
data.
These
studies
suggest
astrocytes
represent
diverse
they
display
brain
area–
disease–specific
properties
functions.
In
review,
we
summarize
these
observations,
emphasize
areas
where
clear
conclusions
can
be
made,
discuss
potential
unifying
themes.
We
also
identify
knowledge
gaps
need
to
addressed
order
exploit
astrocyte
diversity
biological
phenomenon
physiological
relevance
CNS.
thus
provide
summary
perspective
on
vertebrate
Astrocytes,
a
type
of
glia,
are
abundant
and
morphologically
complex
cells.
Here,
we
report
astrocyte
molecular
profiles,
diversity,
morphology
across
the
mouse
central
nervous
system
(CNS).
We
identified
shared
region-specific
astrocytic
genes
functions
explored
cellular
origins
their
regional
diversity.
gene
networks
correlated
with
morphology,
several
which
unexpectedly
contained
Alzheimer’s
disease
(AD)
risk
genes.
CRISPR/Cas9–mediated
reduction
candidate
reduced
morphological
complexity
resulted
in
cognitive
deficits.
The
same
were
down-regulated
human
AD,
an
AD
model
that
displayed
other
brain
disorders.
thus
provide
comprehensive
data
on
diversity
mechanisms
CNS
basis
health
disease.
CNS Neuroscience & Therapeutics,
Год журнала:
2019,
Номер
25(6), С. 665 - 673
Опубликована: Март 30, 2019
Summary
Astrocytes
are
the
most
abundant
glial
cells
in
central
nervous
system
(CNS)
and
participate
synaptic,
circuit,
behavioral
functions.
The
well‐developed
protoplasmic
astrocytes
contain
numerous
processes
forming
well‐delineated
bushy
territories
that
overlap
by
as
little
5%
at
their
boundaries.
This
highly
complex
morphology,
with
up
to
approximately
80%
of
cell's
membrane
constituted
fine
dimensions
on
tens
nanometer
scale
high
surface
area
volume
ratios,
comes
contact
synapses,
blood
vessels,
other
cells.
Recent
progress
is
challenging
conventional
view
morphologically
homogeneous
throughout
brain;
instead,
they
display
circuit‐
region‐specific
morphological
diversity
may
contribute
heterogeneous
astrocyte‐neuron
spatiotemporal
interplay
different
brain
areas.
Further,
structure
found
be
plastic
activity‐dependent.
We
beginning
understand
how
astrocyte
structural
plasticity
contributes
change/loss
traditionally
known
a
hallmark
for
reactive
astrogliosis,
common
pathological
feature
many
neurological
disorders.
However,
recent
data
suggest
deficits
preceding
astrogliosis
drive
disease
progression.
review
summarizes
advances
diversity,
plasticity,
disease‐related
deficits.
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Фев. 12, 2019
Abstract
Adenosine
5′
triphosphate
(ATP)
is
a
universal
intracellular
energy
source
and
an
evolutionarily
ancient,
ubiquitous
extracellular
signal
in
diverse
species.
Here,
we
report
the
generation
characterization
of
single-wavelength
genetically
encoded
fluorescent
sensors
(iATPSnFRs)
for
imaging
cytosolic
ATP
from
insertion
circularly
permuted
superfolder
GFP
into
epsilon
subunit
F
0
1
-ATPase
Bacillus
PS3
.
On
cell
surface
within
cytosol,
iATPSnFR
1.0
responds
to
relevant
concentrations
(30
μM
3
mM)
with
fast
increases
fluorescence.
iATPSnFRs
can
be
targeted
specific
types
sub-cellular
compartments,
imaged
standard
light
microscopes,
do
not
respond
other
nucleotides
nucleosides,
when
fused
red
protein
function
as
ratiometric
indicators.
After
careful
consideration
their
modest
pH
sensitivity,
represent
promising
reagents
space
cells
during
variety
settings,
further
application-specific
refinements.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Окт. 13, 2023
Astroglia
are
a
broad
class
of
neural
parenchymal
cells
primarily
dedicated
to
homoeostasis
and
defence
the
central
nervous
system
(CNS).
contribute
pathophysiology
all
neurological
neuropsychiatric
disorders
in
ways
that
can
be
either
beneficial
or
detrimental
disorder
outcome.
Pathophysiological
changes
astroglia
primary
secondary
result
gain
loss
functions.
respond
external,
non-cell
autonomous
signals
associated
with
any
form
CNS
pathology
by
undergoing
complex
variable
their
structure,
molecular
expression,
function.
In
addition,
internally
driven,
cell
astroglial
innate
properties
lead
pathologies.
Astroglial
is
complex,
different
pathophysiological
states
phenotypes
context-specific
vary
disorder,
disorder-stage,
comorbidities,
age,
sex.
Here,
we
classify
into
(i)
reactive
astrogliosis,
(ii)
atrophy
function,
(iii)
degeneration
death,
(iv)
astrocytopathies
characterised
aberrant
forms
drive
disease.
We
review
across
spectrum
human
diseases
disorders,
including
neurotrauma,
stroke,
neuroinfection,
autoimmune
attack
epilepsy,
as
well
neurodevelopmental,
neurodegenerative,
metabolic
disorders.
Characterising
cellular
mechanisms
represents
new
frontier
identify
novel
therapeutic
strategies.
