Cell Reports,
Год журнала:
2023,
Номер
42(1), С. 111942 - 111942
Опубликована: Янв. 1, 2023
Mutations
in
the
MECP2
gene
underlie
a
spectrum
of
neurodevelopmental
disorders,
most
commonly
Rett
syndrome
(RTT).
We
ask
whether
mutations
interfere
with
human
astrocyte
developmental
maturation,
thereby
affecting
their
ability
to
support
neurons.
Using
human-based
models,
we
show
that
RTT-causing
greatly
impact
key
role
astrocytes
regulating
overall
brain
bioenergetics
and
these
metabolic
aberrations
are
likely
mediated
by
dysfunctional
mitochondria.
During
post-natal
rely
on
neurons
induce
complex
stellate
morphology
transcriptional
changes.
While
cause
cell-intrinsic
landscape,
surprisingly,
they
do
not
affect
neuron-induced
expression.
Notably,
however,
unable
develop
mature
due
cell-
non-cell-autonomous
caused
mutations.
Thus,
critically
cellular
molecular
features
and,
hence,
interact
structural
functional
maturation
Cell Reports,
Год журнала:
2021,
Номер
35(2), С. 108952 - 108952
Опубликована: Апрель 1, 2021
The
mechanisms
controlling
the
post-natal
maturation
of
astrocytes
play
a
crucial
role
in
ensuring
correct
synaptogenesis.
We
show
that
mitochondrial
biogenesis
developing
is
necessary
for
coordinating
astrocyte
and
astrocytic
depends
on
transient
upregulation
metabolic
regulator
peroxisome
proliferator-activated
receptor
gamma
(PPARγ)
co-activator
1α
(PGC-1α),
which
controlled
by
metabotropic
glutamate
5
(mGluR5).
At
tissue
level,
loss
or
downregulation
PGC-1α
sustains
proliferation,
dampens
morphogenesis,
impairs
formation
function
neighboring
synapses,
whereas
its
genetic
re-expression
sufficient
to
restore
mitochondria
compartment
astroglial
synaptic
defects.
Our
findings
developmental
enhancement
critical
mechanism
supporting
synaptogenesis,
thus
suggesting
may
be
therapeutic
target
case
neurodevelopmental
psychiatric
disorders
characterized
impaired
Journal of Neuroinflammation,
Год журнала:
2021,
Номер
18(1)
Опубликована: Дек. 1, 2021
The
brain
is
unique
and
the
most
complex
organ
of
body,
containing
neurons
several
types
glial
cells
different
origins
properties
that
protect
ensure
normal
structure
function.
Neurological
disorders
are
result
a
failure
nervous
system
multifaceted
cellular
networks.
Although
great
progress
has
been
made
in
understanding
glia
involvement
neuropathology,
therapeutic
outcomes
still
not
satisfactory.
Here,
we
discuss
recent
perspectives
on
role
microglia
astrocytes
neurological
disorders,
including
two
common
neurodegenerative
conditions,
Alzheimer
disease
progranulin-related
frontotemporal
lobar
dementia,
as
well
astrocytoma
tumors.
We
emphasize
key
factors
astrocytic
biology
such
highly
heterogeneic
nature
strongly
dependent
environment,
genetic
predispose
to
certain
pathologies
senescence
inevitably
changes
CNS
landscape.
Our
diverse
contributions
diseases
can
lead
advances
their
functional
recovery
after
malfunction.
Journal of Cerebral Blood Flow & Metabolism,
Год журнала:
2022,
Номер
42(5), С. 738 - 745
Опубликована: Янв. 26, 2022
The
energy
cost
of
information
processing
is
thought
to
be
chiefly
neuronal,
with
a
minor
fraction
attributed
glial
cells.
However,
there
compelling
evidence
that
astrocytes
capture
synaptic
K
+
using
their
Na
/K
ATPase,
and
not
solely
through
Kir4.1
channels
as
was
once
thought.
When
this
active
buffering
taken
into
account,
the
rises
by
>200%.
Gram-per-gram,
turn
out
expensive
neurons.
This
conclusion
supported
3D
reconstruction
neuropil
showing
similar
mitochondrial
densities
in
neurons
astrocytes,
cell-specific
transcriptomics
proteomics,
rates
tricarboxylic
acid
cycle.
Possible
consequences
for
reactive
astrogliosis
brain
disease
are
discussed.
Cell Reports,
Год журнала:
2023,
Номер
42(1), С. 111942 - 111942
Опубликована: Янв. 1, 2023
Mutations
in
the
MECP2
gene
underlie
a
spectrum
of
neurodevelopmental
disorders,
most
commonly
Rett
syndrome
(RTT).
We
ask
whether
mutations
interfere
with
human
astrocyte
developmental
maturation,
thereby
affecting
their
ability
to
support
neurons.
Using
human-based
models,
we
show
that
RTT-causing
greatly
impact
key
role
astrocytes
regulating
overall
brain
bioenergetics
and
these
metabolic
aberrations
are
likely
mediated
by
dysfunctional
mitochondria.
During
post-natal
rely
on
neurons
induce
complex
stellate
morphology
transcriptional
changes.
While
cause
cell-intrinsic
landscape,
surprisingly,
they
do
not
affect
neuron-induced
expression.
Notably,
however,
unable
develop
mature
due
cell-
non-cell-autonomous
caused
mutations.
Thus,
critically
cellular
molecular
features
and,
hence,
interact
structural
functional
maturation
