Brain Research Bulletin,
Год журнала:
2025,
Номер
227, С. 111411 - 111411
Опубликована: Май 29, 2025
Autism
Spectrum
Disorder
(ASD)
is
a
neurodevelopmental
condition
marked
by
difficulties
in
social
communication,
languages,
and
repetitive
behaviors.
Its
rising
prevalence
has
made
it
critical
global
public
health
issue.
ASD
believed
to
arise
from
combination
of
genetic
environmental
influences.
While
some
gene
mutations
associated
with
have
been
identified,
most
cases
lack
clear
explanations.
Evidence
increasingly
points
early-life
factors
as
key
contributors
ASD,
including
advanced
parental
age,
maternal
diabetes
during
pregnancy,
infections,
hormonal
imbalances,
certain
medications,
exposure
air
pollution.
Currently,
diagnosis
relies
on
behavioral
assessments,
but
the
absence
specific
molecular
biomarkers
poses
significant
obstacles
early
detection
targeted
therapies.
Encouragingly,
research
identified
potential
biomarkers,
such
neuroimaging
classifiers,
electroencephalography
patterns,
eye-tracking
data,
digital
analytics,
expression
profiles,
inflammatory
chemokine
markers,
proteomic
metabolomic
gut
microbiota
characteristics.
Potential
therapeutical
strategies
under
investigation
include
therapies,
non-invasive
brain
stimulation,
antioxidants,
oxytocin,
AVPR1a
antagonists,
PPAR
agonists,
mTOR
inhibitors.
This
review
explores
across
five
areas:
epidemiological
trends,
mechanisms,
their
roles,
diagnostic
therapeutic
approaches.
Highlights•Perturb-FISH
combines
spatial
transcriptomics
and
readout
of
CRISPR
perturbation•We
recover
the
effects
genetic
perturbation
on
transcriptome
single
cells•We
find
specific
networks
related
to
cell
neighbors
in
tissue•We
connect
time-resolved
imaging
phenotypes
after
perturbationSummaryPooled
optical
screens
have
enabled
study
cellular
interactions,
morphology,
or
dynamics
at
massive
scale,
but
they
not
yet
leveraged
power
highly
plexed
single-cell
resolved
transcriptomic
readouts
inform
molecular
pathways.
Here,
we
present
a
combination
with
parallel
detection
situ
amplified
guide
RNAs
(Perturb-FISH).
Perturb-FISH
recovers
intracellular
that
are
consistent
RNA-sequencing-based
(Perturb-seq)
screen
lipopolysaccharide
response
cultured
monocytes,
it
uncovers
intercellular
density-dependent
regulation
innate
immune
response.
Similarly,
three-dimensional
xenograft
models,
identifies
tumor-immune
interactions
altered
by
knockout.
When
paired
functional
separate
autism
spectrum
disorder
risk
genes
human-induced
pluripotent
stem
(hIPSC)
astrocytes,
shows
common
calcium
activity
their
associated
dysregulated
is
thus
general
method
for
studying
associations
biology
resolution.Graphical
abstract
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
17
Опубликована: Янв. 11, 2024
Oligodendrocytes
play
a
crucial
role
in
our
central
nervous
system
(CNS)
by
myelinating
axons
for
faster
action
potential
conduction,
protecting
from
degeneration,
structuring
the
position
of
ion
channels,
and
providing
nutrients
to
neurons.
Oligodendrocyte
dysfunction
and/or
dysmyelination
can
contribute
range
neurodegenerative
diseases
neuropsychiatric
disorders
such
as
Multiple
Sclerosis
(MS),
Leukodystrophy
(LD),
Schizophrenia
(SCZ),
Autism
Spectrum
Disorder
(ASD).
Common
characteristics
identified
across
these
were
either
an
inability
oligodendrocytes
remyelinate
after
degeneration
or
defects
oligodendrocyte
development
maturation.
Unfortunately,
causal
mechanisms
are
still
uncertain,
therapeutic
targets
remain
elusive.
Many
studies
rely
on
use
animal
models
identify
molecular
cellular
behind
disorders,
however,
face
species-specific
challenges
therefore
lack
translatability.
The
human
induced
pluripotent
stem
cells
(hiPSCs)
model
neurological
is
becoming
powerful
new
tool,
improving
understanding
pathophysiology
capacity
explore
targets.
Here,
we
focus
application
hiPSC-derived
systems
caused
dysregulation.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 2, 2025
Cortical
layer
5
(L5)
intratelencephalic
(IT)
and
pyramidal
tract
(PT)
neurons
are
embedded
in
distinct
information
processing
pathways.
Their
morphology,
connectivity,
electrophysiological
properties,
role
behavior
have
been
extensively
analyzed.
However,
the
molecular
composition
of
their
synapses
remains
largely
uncharacterized.
Here,
we
dissect
protein
excitatory
postsynaptic
compartment
mouse
L5
intact
somatosensory
circuits,
using
an
optimized
proximity
biotinylation
workflow
with
high
spatial
accuracy.
We
find
synaptic
signatures
IT
PT
that
defined
by
proteins
regulating
organization
transmission,
including
cell-surface
(CSPs),
neurotransmitter
receptors
ion
channels.
In
addition,
a
differential
vulnerability
to
disease,
marked
enrichment
autism
risk
genes
signature
compared
neurons.
These
results
align
human
studies
suggest
is
susceptible
autism.
Our
approach
versatile
can
be
broadly
applied
other
neuron
types
create
protein-based,
atlas
cortical
circuits.
Authors
use
proteomics
reporting
disease
vulnerabilities.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 28, 2025
Abstract
Astrocytes
participate
in
neuronal
synaptic
programs
that
are
enriched
for
genetic
associations
schizophrenia
and
autism
spectrum
disorders
(ASD).
To
better
understand
how
these
co-regulated
cellular
induced
during
early
development,
we
studied
astrocytes
iPSC-derived
neurons
co-cultures
mono-cultures
at
16
time
points
spanning
0.5
hours
to
8
days.
We
found
upregulation
of
genes
involved
cholesterol
biosynthesis
preceded
the
activation
gene
astrocytic
Nrxn1
.
Neuronal
knockdown
key
receptors
led
downregulation
a
robust
transcriptional
response
astrocytes,
including
further
This
suggests
astrocyte-supplied
drives
changes
bi-directional
signalling
is
occuring.
The
upregulated
were
deleterious
variants
neurodevelopmental
disorders,
suggesting
their
pathogenic
effect
may
be,
part,
mediated
by
reduced
buffering
capacity
astrocyte
supply
neurons.
These
findings
highlight
critical
role
astrocyte-neuron
interactions
psychiatric
particularly
relation
lipid
metabolism
plasticity.
Molecular Psychiatry,
Год журнала:
2024,
Номер
29(12), С. 3950 - 3961
Опубликована: Июнь 15, 2024
Substance
use
disorders
(SUD)
and
drug
addiction
are
major
threats
to
public
health,
impacting
not
only
the
millions
of
individuals
struggling
with
SUD,
but
also
surrounding
families
communities.
One
seminal
challenges
in
treating
studying
human
populations
is
high
prevalence
co-morbid
conditions,
including
an
increased
risk
contracting
a
immunodeficiency
virus
(HIV)
infection.
Of
~15
million
people
who
inject
drugs
globally,
17%
persons
HIV.
Conversely,
HIV
factor
for
SUD
because
chronic
pain
syndromes,
often
encountered
HIV,
can
lead
opioid
medications
that
turn
increase
addiction.
We
hypothesize
exert
shared
effects
on
brain
cell
types,
adaptations
related
neuroplasticity,
neurodegeneration,
neuroinflammation.
Basic
research
needed
refine
our
understanding
these
affected
types
adaptations.
Studying
context
at
single-cell
level
represents
compelling
strategy
understand
reciprocal
interactions
among
both
made
feasible
by
availability
large,
extensively-phenotyped
tissue
collections
have
been
amassed
Neuro-HIV
community.
In
addition,
sophisticated
animal
models
developed
conditions
provide
means
precisely
evaluate
specific
exposures
stages
disease.
propose
genomics
uniquely
powerful
technology
characterize
brain,
integrating
data
from
cohorts
models.
formed
Single-Cell
Opioid
Responses
Context
(SCORCH)
consortium
carry
out
this
strategy.
Life Sciences,
Год журнала:
2024,
Номер
354, С. 122952 - 122952
Опубликована: Авг. 9, 2024
The
bidirectional
regulation
between
the
gut
microbiota
and
brain,
known
as
gut-brain
axis,
has
received
significant
attention.
myelin
sheath,
produced
by
oligodendrocytes
or
Schwann
cells,
is
essential
for
efficient
nervous
signal
transmission
maintenance
of
brain
function.
Growing
evidence
shows
that
both
oligodendrogenesis
myelination
are
modulated
its
metabolites,
when
dysbiosis
occurs,
changes
in
composition
and/or
associated
metabolites
may
impact
developmental
occurrence
neurodevelopmental
disabilities.
Although
link
demyelinating
disease
such
multiple
sclerosis
been
extensively
studied,
our
knowledge
about
role
other
myelin-related
disorders,
neurodegenerative
diseases,
limited.
Mechanistically,
microbiota-oligodendrocyte
axis
primarily
mediated
factors
inflammation,
vagus
nerve,
endocrine
hormones,
evidenced
metagenomics,
metabolomics,
vagotomy,
morphological
molecular
approaches.
Treatments
targeting
this
include
probiotics,
prebiotics,
microbial
herbal
bioactive
compounds,
specific
dietary
management.
In
addition
to
commonly
used
approaches,
viral
vector-mediated
tracing
gene
manipulation,
integrated
multiomics
multicenter
clinical
trials
will
greatly
promote
mechanistic
interventional
studies
ultimately,
development
new
preventive
therapeutic
strategies
against
gut-oligodendrocyte
axis-mediated
impairments.
Interestingly,
recent
findings
showed
can
be
induced
hippocampal
damage
reversible
myelin-targeted
drugs,
which
provides
insights
into
understanding
how
hippocampus-based
functional
impairment
(such
Alzheimer's
disease)
regulates
peripheral
homeostasis
systemic
disorders.