Molecular Psychiatry,
Год журнала:
2023,
Номер
28(4), С. 1611 - 1621
Опубликована: Март 13, 2023
Abstract
Clinical
and
animal
studies
have
shown
that
gut
microbiome
disturbances
can
affect
neural
function
behaviors
via
the
microbiota–gut–brain
axis,
may
be
implicated
in
pathogenesis
of
several
brain
diseases.
However,
exactly
how
modulates
nervous
system
activity
remains
obscure.
Here,
using
a
single-cell
nucleus
sequencing
approach,
we
sought
to
characterize
cell
type–specific
transcriptomic
changes
prefrontal
cortex
hippocampus
derived
from
germ-free
(GF),
specific
pathogen
free,
colonized-GF
mice.
We
found
absence
microbiota
resulted
cell-specific
changes.
Furthermore,
microglia
transcriptomes
were
preferentially
influenced,
which
could
effectively
reversed
by
microbial
colonization.
Significantly,
modulated
mutual
transformation
microglial
subpopulations
two
regions.
Cross-species
analysis
showed
transcriptome
these
mainly
associated
with
Alzheimer’s
disease
(AD)
major
depressive
disorder
(MDD),
further
supported
behavioral
tests.
Our
findings
demonstrate
modulate
subtypes,
lead
new
insights
into
AD
MDD.
Cell,
Год журнала:
2022,
Номер
185(14), С. 2452 - 2468.e16
Опубликована: Июнь 13, 2022
COVID
survivors
frequently
experience
lingering
neurological
symptoms
that
resemble
cancer-therapy-related
cognitive
impairment,
a
syndrome
for
which
white
matter
microglial
reactivity
and
consequent
neural
dysregulation
is
central.
Here,
we
explored
the
neurobiological
effects
of
respiratory
SARS-CoV-2
infection
found
white-matter-selective
in
mice
humans.
Following
mild
mice,
persistently
impaired
hippocampal
neurogenesis,
decreased
oligodendrocytes,
myelin
loss
were
evident
together
with
elevated
CSF
cytokines/chemokines
including
CCL11.
Systemic
CCL11
administration
specifically
caused
neurogenesis.
Concordantly,
humans
lasting
post-COVID
exhibit
levels.
Compared
SARS-CoV-2,
influenza
similar
patterns
reactivity,
oligodendrocyte
loss,
at
early
time
points,
but
after
influenza,
only
pathology
persisted.
These
findings
illustrate
neuropathophysiology
cancer
therapy
may
contribute
to
impairment
following
even
COVID.
Neuron,
Год журнала:
2022,
Номер
110(21), С. 3484 - 3496
Опубликована: Окт. 7, 2022
Persistent
neurological
and
neuropsychiatric
symptoms
affect
a
substantial
fraction
of
people
after
COVID-19
represent
major
component
the
post-acute
syndrome,
also
known
as
long
COVID.
Here,
we
review
what
is
understood
about
pathobiology
impact
on
CNS
discuss
possible
neurobiological
underpinnings
cognitive
affecting
survivors.
We
propose
chief
mechanisms
that
may
contribute
to
this
emerging
health
crisis.
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.
Nature,
Год журнала:
2023,
Номер
622(7981), С. 120 - 129
Опубликована: Сен. 6, 2023
Abstract
Multimodal
astrocyte–neuron
communications
govern
brain
circuitry
assembly
and
function
1
.
For
example,
through
rapid
glutamate
release,
astrocytes
can
control
excitability,
plasticity
synchronous
activity
2,3
of
synaptic
networks,
while
also
contributing
to
their
dysregulation
in
neuropsychiatric
conditions
4–7
communicate
fast
focal
they
should
possess
an
apparatus
for
Ca
2+
-dependent
exocytosis
similar
neurons
8–10
However,
the
existence
this
mechanism
has
been
questioned
11–13
owing
inconsistent
data
14–17
a
lack
direct
supporting
evidence.
Here
we
revisited
astrocyte
hypothesis
by
considering
emerging
molecular
heterogeneity
18–21
using
molecular,
bioinformatic
imaging
approaches,
together
with
cell-specific
genetic
tools
that
interfere
vivo.
By
analysing
existing
single-cell
RNA-sequencing
databases
our
patch-seq
data,
identified
nine
molecularly
distinct
clusters
hippocampal
astrocytes,
among
which
found
notable
subpopulation
selectively
expressed
synaptic-like
glutamate-release
machinery
localized
discrete
sites.
Using
GluSnFR-based
22
situ
vivo,
corresponding
subgroup
responds
reliably
astrocyte-selective
stimulations
subsecond
release
events
at
spatially
precise
hotspots,
were
suppressed
astrocyte-targeted
deletion
vesicular
transporter
(VGLUT1).
Furthermore,
or
its
isoform
VGLUT2
revealed
specific
contributions
glutamatergic
cortico-hippocampal
nigrostriatal
circuits
during
normal
behaviour
pathological
processes.
uncovering
atypical
specialized
adult
brain,
provide
insights
into
complex
roles
central
nervous
system
(CNS)
physiology
diseases,
identify
potential
therapeutic
target.
