Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids
Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(21)
Published: March 28, 2024
Understanding
the
impact
of
long-term
opioid
exposure
on
embryonic
brain
is
critical
due
to
surging
number
pregnant
mothers
with
dependency.
However,
this
has
been
limited
by
human
inaccessibility
and
cross-species
differences
in
animal
models.
Here,
a
midbrain
model
established
that
uses
hiPSC-derived
organoids
assess
cell-type-specific
responses
acute
chronic
fentanyl
treatment
withdrawal.
Single-cell
mRNA
sequencing
25,510
cells
from
different
groups
reveals
arrests
neuronal
subtype
specification
during
early
development
alters
synaptic
activity
neuron
projection.
In
contrast,
increases
dopamine
release
but
does
not
significantly
alter
gene
expression
related
cell
lineage
development.
These
results
provide
first
examination
effects
at
single-cell
level.
Language: Английский
Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology
Ila Dwivedi,
No information about this author
Gabriel G. Haddad
No information about this author
Frontiers in Cellular Neuroscience,
Journal Year:
2024,
Volume and Issue:
18
Published: May 15, 2024
Over
the
past
two
decades,
Opioid
Use
Disorder
(OUD)
among
pregnant
women
has
become
a
major
global
public
health
concern.
OUD
been
characterized
as
problematic
pattern
of
opioid
use
despite
adverse
physical,
psychological,
behavioral,
and
or
social
consequences.
Due
to
relapsing–remitting
nature
this
disorder,
mothers
are
chronically
exposed
exogenous
opioids,
resulting
in
neurological
neuropsychiatric
outcomes.
Collateral
fetal
exposure
opioids
also
precipitates
severe
neurodevelopmental
neurocognitive
sequelae.
At
present,
much
what
is
known
regarding
neurobiological
consequences
prenatal
(POE)
derived
from
preclinical
studies
animal
models
postnatal
postmortem
investigations
humans.
However,
species-specific
differences
brain
development,
variations
subject
age/health/background,
disparities
sample
collection
storage
have
complicated
interpretation
findings
produced
by
these
explorations.
The
ethical
logistical
inaccessibility
human
tissue
limited
direct
examinations
drug
effects.
To
circumvent
confounding
factors,
recent
groups
begun
employing
induced
pluripotent
stem
cell
(iPSC)-derived
organoid
technology,
which
provides
access
key
aspects
cellular
molecular
structure,
function
vitro
.
In
review,
we
endeavor
encapsulate
advancements
culture
that
enabled
scientists
model
dissect
neural
underpinnings
effects
POE.
We
hope
not
only
emphasize
utility
organoids
for
investigating
conditions,
but
highlight
opportunities
further
technical
conceptual
progress.
Although
application
critical
field
research
still
its
nascent
stages,
understanding
neurobiology
POE
via
modality
will
provide
insights
improving
maternal
Language: Английский
Cocaine perturbs neurodevelopment and increases neuroinflammation in a prenatal cerebral organoid model
Translational Psychiatry,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: March 26, 2025
Prenatal
exposure
to
cocaine
causes
abnormalities
in
foetal
brain
development,
which
are
linked
later
development
of
anxiety,
depression
and
cognitive
dysfunction.
Previous
studies
rodent
models
have
indicated
that
prenatal
affects
proliferation,
differentiation
connectivity
neural
cell
types.
Here,
using
cerebral
organoids
derived
from
the
human
iPSC
line
HPSI1213i-babk_2,
we
investigated
cocaine-induced
changes
gene
expression
regulatory
landscape
at
an
early
developmental
time
point,
leveraging
recent
advances
single
RNA-seq
ATAC-seq.
iPSC-cerebral
replicated
well-established
responses
observed
vivo
provided
additional
information
about
cell-type
specific
regulation
following
exposure.
Cocaine
altered
patterns,
part
through
epigenetic
remodelling,
revealed
disordered
plasticity
mechanisms
organoids.
Perturbed
neurodevelopmental
cellular
signalling
inflammatory-like
activation
astrocyte
populations
were
also
evident
The
combination
neuroplasticity,
neurodevelopment
neuroinflammatory
suggests
can
mediate
substantial
disruption
normal
maturation
brain.
These
findings
offer
new
insights
into
mechanism
underlying
adverse
effects
on
point
possible
pathomechanisms
neuropsychiatric
disturbances.
Language: Английский
A human iPSC-derived midbrain neural stem cell model of prenatal opioid exposure and withdrawal: A proof of concept study
PLoS ONE,
Journal Year:
2025,
Volume and Issue:
20(4), P. e0319418 - e0319418
Published: April 1, 2025
A
growing
body
of
clinical
literature
has
described
neurodevelopmental
delays
in
infants
with
chronic
prenatal
opioid
exposure
and
withdrawal.
Despite
this,
the
mechanism
how
opioids
impact
developing
brain
remains
unknown.
Here,
we
developed
an
vitro
model
morphine
withdrawal
using
healthy
human
induced
pluripotent
stem
cell
(iPSC)-derived
midbrain
neural
progenitors
monolayer.
To
optimize
our
model,
identified
that
a
longer
induction
regional
patterning
period
increases
expression
canonical
receptors
mu
kappa
compared
to
shorter
protocol
(
OPRM1
,
two-tailed
t-test,
p
=
0.004;
OPRK1
0.0003).
Next,
showed
derived
from
iPSC
also
have
scant
toll-like
receptor
4
(TLR4)
expression,
key
player
neonatal
syndrome
pathophysiology.
During
withdrawal,
differentiating
experience
cyclic
adenosine
monophosphate
overshoot
exposed
vehicle
0.0496)
conditions
0.0136,
1-way
ANOVA).
Finally,
alters
proportions
differentiated
progenitor
fates
(2-way
ANOVA,
F
16.05,
<
0.0001).
Chronic
increased
nestin
positive
0.0094),
decreased
neuronal
nuclear
antigen
neurons
(NEUN)
0.0047)
those
vehicle.
Morphine
glial
fibrillary
acidic
protein
cells
astrocytic
lineage
0.044),
NEUN-positive
0.0001)
only.
Applications
this
paradigm
include
mechanistic
studies
underscoring
fate
commitments
early
neurodevelopment
during
Language: Английский
Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights
Microbial Biotechnology,
Journal Year:
2024,
Volume and Issue:
17(10)
Published: Oct. 1, 2024
The
widespread
use
of
opioids
for
chronic
pain
management
not
only
poses
a
significant
public
health
issue
but
also
contributes
to
the
risk
tolerance,
dependence,
and
addiction,
leading
opioid
disorder
(OUD),
which
affects
millions
globally
each
year.
Recent
research
has
highlighted
potential
bidirectional
relationship
between
gut
microbiome
OUD.
This
emerging
perspective
is
critical,
especially
as
epidemic
intensifies,
emphasizing
need
investigate
how
OUD
may
alter
dynamics
vice
versa.
Understanding
these
interactions
could
reveal
new
insights
into
mechanisms
addiction
well
provide
novel
approaches
managing
potentially
mitigating
impacts.
comprehensive
review
explores
intricate
link
through
gut-brain
axis,
focusing
on
opiates
influence
microbial
composition,
functional
changes,
mucosal
integrity.
By
synthesizing
current
findings,
aims
inspire
strategies
combat
crisis
leverage
microbiome-centred
interventions
preventing
treating
Language: Английский
Unraveling the Effects of Prenatal Anesthesia on Neurodevelopment: A Review of Current Evidence and Future Directions
Qiu‐Xia Xiao,
No information about this author
Min‐Jian Geng,
No information about this author
Qiulin Wang
No information about this author
et al.
NeuroToxicology,
Journal Year:
2024,
Volume and Issue:
105, P. 96 - 110
Published: Sept. 12, 2024
Language: Английский
Recent advances in brain organoids: a comprehensive review of the last eight years
New discovery.,
Journal Year:
2024,
Volume and Issue:
unknown, P. 1 - 14
Published: Oct. 31, 2024
Organoids
are
three-dimensional
cellular
structures
grown
in
vitro
that
can
self-organize
and
differentiate
into
cell
types
with
organ-specific
functions,
closely
mimicking
the
biological
properties
of
tissues
organs
vivo.
Brain
organoids,
which
resembling
brain
function,
serve
as
valuable
models
for
medical
research,
including
disease
microenvironment
simulation,
mechanism
exploration,
drug
evaluation.
In
this
review,
we
analyzed
808
articles
retrieved
from
PubMed,
CNKI,
Wanfang
databases
using
keyword
"brain
organoids,"
180
were
included.
We
summarized
research
progress
organoids
over
past
eight
years
by
categorizing
refining
findings.
Our
analysis
shows
have
achieved
significant
success
simulating
development
vitro,
leading
to
establishment
refinement
3D
organoid
research.
been
widely
applied
explore
disease-related
mechanisms,
yielding
promising
results
opening
avenues
further
on
human
brain.
summarize
three
areas:
culture
methods,
exploration.
Language: Английский