Archives of Toxicology,
Journal Year:
2024,
Volume and Issue:
98(5), P. 1271 - 1295
Published: March 13, 2024
Abstract
Adult
neurotoxicity
(ANT)
and
developmental
(DNT)
assessments
aim
to
understand
the
adverse
effects
underlying
mechanisms
of
toxicants
on
human
nervous
system.
In
recent
years,
there
has
been
an
increasing
focus
so-called
new
approach
methodologies
(NAMs).
The
Organization
for
Economic
Co-operation
Development
(OECD),
together
with
European
American
regulatory
agencies,
promote
use
validated
alternative
test
systems,
but
date,
guidelines
DNT
ANT
assessment
rely
primarily
classical
animal
testing.
Alternative
methods
include
both
non-animal
approaches
systems
non-vertebrates
(e.g.,
nematodes)
or
non-mammals
fish).
Therefore,
this
review
summarizes
advances
NAMs
focusing
highlights
potential
current
critical
issues
full
implementation
these
in
future.
status
vitro
battery
(DNT
IVB)
is
also
reviewed
as
a
first
step
context.
Critical
such
(i)
need
batteries
method
integration
(from
silico
vivo
alternatives,
e.g.,
zebrafish,
C.
elegans
)
requiring
interdisciplinarity
manage
complexity,
(ii)
interlaboratory
transferability,
(iii)
urgent
validation
are
discussed.
Molecular Psychiatry,
Journal Year:
2024,
Volume and Issue:
29(9), P. 2622 - 2633
Published: March 22, 2024
Several
lines
of
evidence
indicate
the
involvement
neuroinflammatory
processes
in
pathophysiology
schizophrenia
(SCZ).
Microglia
are
brain
resident
immune
cells
responding
toward
invading
pathogens
and
injury-related
products,
additionally,
have
a
critical
role
improving
neurogenesis
synaptic
functions.
Aberrant
activation
microglia
SCZ
is
one
leading
hypotheses
for
disease
pathogenesis,
but
due
to
lack
proper
human
cell
models,
not
well
studied.
We
used
monozygotic
twins
discordant
healthy
individuals
generate
induced
pluripotent
stem
cell-derived
assess
transcriptional
functional
differences
between
controls,
affected
unaffected
twins.
The
from
had
increased
expression
several
common
inflammation-related
genes
compared
individuals.
also
reduced
response
interleukin
1
beta
(IL1β)
treatment,
no
significant
migration
or
phagocytotic
activity.
Ingenuity
Pathway
Analysis
(IPA)
showed
abnormalities
related
extracellular
matrix
signaling.
RNA
sequencing
predicted
downregulation
structure
constituent
Gene
Ontology
(GO)
terms
hepatic
fibrosis
pathway
that
were
shared
by
both
twins,
upregulation
major
histocompatibility
complex
(MHC)
class
II
receptors
was
observed
only
twin
microglia.
Also,
heterogeneous
clozapine,
minocycline,
sulforaphane
treatments.
Overall,
despite
inflammatory
genes,
we
clear
signs
hyperactivation
patients
with
SCZ.
conclude
gene
aberrations
inflammation
without
contributing
microglial
activation.
Frontiers in Neuroanatomy,
Journal Year:
2025,
Volume and Issue:
18
Published: Jan. 3, 2025
While
widefield
microscopy
has
long
been
constrained
by
out-of-focus
scattering,
advancements
have
generated
a
solution
in
the
form
of
confocal
laser
scanning
(cLSM)
and
optical
sectioning
using
structured
illumination
(OSM).
In
this
study,
we
aim
to
investigate,
microglia
branching,
if
cLSM
OSM
can
produce
images
with
comparable
morphological
characteristics.
By
imaging
somatosensory
from
tissue
slice
3-week-old
mouse
establishing
parameters
that
characterizes
microglial
branching
pattern,
were
able
show
there
is
no
difference
total
length
branch
tree,
number
branches,
mean
primary
terminal
branches.
We
did
find
area-based
such
as
occupied
area
surveillance
bigger
isolated
compared
ones.
Additionally,
investigating
acquisition
time
between
techniques
personal
costs
establish
amortization
could
be
made
6.11
±
2.93
years
case
countries
Human
Development
Index
(HDI)
=
7-9
7.06
3.13
years,
respectably,
for
HDI
<
7.
As
such,
systems
seem
valid
option
one
just
wants
basic
histological
evaluation,
should
considered
groups
demand
higher
resolution
or
volumetric
images.
Cells,
Journal Year:
2021,
Volume and Issue:
11(1), P. 124 - 124
Published: Dec. 30, 2021
Human
cerebral
organoids,
derived
from
induced
pluripotent
stem
cells,
offer
a
unique
in
vitro
research
window
to
the
development
of
cortex.
However,
key
player
developing
brain,
microglia,
do
not
natively
emerge
organoids.
Here
we
show
that
erythromyeloid
progenitors
(EMPs),
differentiated
migrate
and
mature
into
microglia-like
cells
interact
with
synaptic
material.
Patch-clamp
electrophysiological
recordings
population
supported
emergence
more
diversified
neuronal
phenotypes
displaying
repetitive
firing
action
potentials,
low-threshold
spikes
activity,
while
multielectrode
array
revealed
spontaneous
bursting
activity
increased
power
gamma-band
oscillations
upon
pharmacological
challenge
NMDA.
To
conclude,
within
organoids
promote
network
maturation
recapitulate
some
aspects
microglia-neuron
co-development
vivo,
indicating
could
be
useful
biorealistic
human
platform
for
studying
interactions.
Development,
Journal Year:
2022,
Volume and Issue:
149(8)
Published: April 15, 2022
ABSTRACT
It
has
recently
emerged
that
microglia,
the
tissue-resident
macrophages
of
central
nervous
system,
play
significant
non-innate
immune
roles
to
support
development,
maintenance,
homeostasis
and
repair
brain.
Apart
from
being
highly
specialized
brain
phagocytes,
microglia
modulate
development
functions
neurons
glial
cells
through
both
direct
indirect
interactions.
Thus,
recognizing
elements
influence
heterogeneity
in
normal
is
crucial
understanding
mechanisms
lead
early
disease
pathogenesis
neurodevelopmental
disorders.
In
this
Review,
we
discuss
recent
studies
have
elucidated
physiological
summarize
our
knowledge
their
tissue
repair.
Ecotoxicology and Environmental Safety,
Journal Year:
2022,
Volume and Issue:
235, P. 113429 - 113429
Published: March 21, 2022
Tremendous
progress
has
been
made
in
the
field
of
toxicology
leading
to
advance
developmental
toxicity
assessment.
Conventional
animal
models
and
vitro
two-dimensional
cannot
accurately
describe
toxic
effects
predict
actual
vivo
responses
due
obvious
inter-species
differences
between
humans
animals,
as
well
lack
a
physiologically
relevant
tissue
microenvironment.
Human
embryonic
stem
cell
(hESC)-
induced
pluripotent
(iPSC)-derived
three-dimensional
organoids
are
ideal
complex
multicellular
organotypic
models,
which
indispensable
recapitulating
morphogenesis,
cellular
interactions,
molecular
processes
early
human
organ
development.
Recently,
have
used
for
drug
discovery,
chemical
safety
This
review
discusses
recent
advances
use
organoid
(i.e.,
brain,
retinal,
cardiac,
liver,
kidney,
lung,
intestinal
models)
teratogenicity
assessment
distinct
tissues/organs
following
exposure
pharmaceutical
compounds,
heavy
metals,
persistent
organic
pollutants,
nanomaterials,
ambient
air
pollutants.
Combining
next-generation
with
innovative
engineering
technologies
generates
novel
powerful
tools
assessment,
rapid
this
is
expected
continue.
Trends in Molecular Medicine,
Journal Year:
2023,
Volume and Issue:
29(8), P. 659 - 672
Published: June 22, 2023
Progression
of
Alzheimer's
disease
(AD)
entails
deterioration
or
aberrant
function
multiple
brain
cell
types,
eventually
leading
to
neurodegeneration
and
cognitive
decline.
Defining
how
complex
cell-cell
interactions
become
dysregulated
in
AD
requires
novel
human
cell-based
vitro
platforms
that
could
recapitulate
the
intricate
cytoarchitecture
diversity
brain.
Brain
organoids
(BOs)
are
3D
self-organizing
tissues
partially
resemble
architecture
can
AD-relevant
pathology.
In
this
review,
we
highlight
versatile
applications
different
types
BOs
model
pathogenesis,
including
amyloid-β
tau
aggregation,
neuroinflammation,
myelin
breakdown,
vascular
dysfunction,
other
phenotypes,
as
well
accelerate
therapeutic
development
for
AD.
Neural Regeneration Research,
Journal Year:
2023,
Volume and Issue:
0(0), P. 0 - 0
Published: Jan. 1, 2023
At
the
level
of
in
vitro
drug
screening,
development
a
phenotypic
analysis
system
with
high-content
screening
at
core
provides
strong
platform
to
support
high-throughput
screening.
There
are
few
systematic
reports
on
brain
organoids,
as
new
three-dimensional
model,
terms
model
stability,
key
fingerprint,
and
schemes,
particularly
regarding
strategies
for
massive
numbers
traditional
Chinese
medicine
monomers.
This
paper
reviews
organoids
advantages
over
induced
neurons
or
cells
simulated
diseases.
The
also
highlights
prospects
from
induction
criteria
schemes
based
characteristics
application
system.