bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 5, 2024
Abstract
Although
targeted
radiotherapy
(RT)
is
integral
to
the
increasing
survival
of
cancer
patients,
it
has
significant
side-effects,
cellular
and
molecular
mechanisms
which
are
not
fully
understood.
During
RT
epigenetic
changes
occur
in
neoplastic
tissue,
but
few
studies
have
assessed
these
non-neoplastic
tissue
results
highly
variable.
Using
bulk
DNA
methylation
RNA
sequencing
as
well
spatial
transcriptomics
(ST)
a
unique
cohort
patient
samples,
we
show
distinct
differences
patterns
irradiated
brain
whilst
ST
characterisation
identifies
specific
micro-environmental
niches
present
after
irradiation
highlights
neuropeptides
that
could
be
propagating
neuroinflammation.
We
also
cerebral
organoid
(CO)
model
early
neurons
there
similar
alterations
disruption
machinery,
suggesting
persistent
dysregulation
plays
role
neurotoxicity.
provide
link
between
induced
neuroinflammation
for
first
time
suggest
possible
driving
this
chronic
Neuropsychopharmacology,
Journal Year:
2023,
Volume and Issue:
49(1), P. 3 - 9
Published: Aug. 15, 2023
Abstract
In
contrast
to
most
fields
of
medicine,
progress
discover
and
develop
new
improved
psychiatric
drugs
has
been
slow
disappointing.
The
vast
majority
currently
prescribed
treat
schizophrenia,
mood
anxiety
disorders
are
arguably
no
more
effective
than
the
first
generation
introduced
well
over
50
years
ago.
With
only
a
few
exceptions
current
work
via
same
fundamental
mechanisms
action
as
first-generation
agents.
Here
we
describe
reasons
for
this
outline
number
areas
research
that
involve
greater
reliance
on
experimental
therapeutics
utilizing
recent
advances
in
neuroscience
better
understand
disease
biology.
We
exemplify
potential
impact
these
focus
with
several
examples
novel
agents
have
emerged
which
support
our
optimism
newer,
tolerated
agents,
horizon.
Together
existing
newer
could
offer
markedly
functional
outcomes
millions
people
still
disabled
by
disorders.
Frontiers in Molecular Neuroscience,
Journal Year:
2023,
Volume and Issue:
16
Published: Aug. 3, 2023
Neurodegenerative
diseases
are
adult-onset
neurological
conditions
that
notoriously
difficult
to
model
for
drug
discovery
and
development
because
most
models
unable
accurately
recapitulate
pathology
in
disease-relevant
cells,
making
it
extremely
explore
the
potential
mechanisms
underlying
neurodegenerative
diseases.
Therefore,
alternative
of
human
or
animal
cells
have
been
developed
bridge
gap
allow
impact
new
therapeutic
strategies
be
anticipated
more
by
trying
mimic
neuronal
glial
cell
interactions
many
mechanisms.
In
tandem
with
emergence
human-induced
pluripotent
stem
which
were
first
generated
2007,
accessibility
(hiPSC)
derived
from
patients
can
differentiated
into
neurons,
providing
an
unrivaled
platform
Frontiers in Neuroscience,
Journal Year:
2024,
Volume and Issue:
18
Published: March 5, 2024
Cerebral
organoids,
self-organizing
structures
with
increased
cellular
diversity
and
longevity,
have
addressed
shortcomings
in
mimicking
human
brain
complexity
architecture.
However,
imaging
intact
organoids
poses
challenges
due
to
size,
density,
light-scattering
properties.
Traditional
one-photon
microscopy
faces
limitations
resolution
contrast,
especially
for
deep
regions.
Here,
we
first
discuss
the
fundamentals
of
multiphoton
(MPM)
as
a
promising
alternative,
leveraging
non-linear
fluorophore
excitation
longer
wavelengths
improved
live
cerebral
organoids.
Then,
review
recent
applications
MPM
studying
morphogenesis
differentiation,
emphasizing
its
potential
overcoming
associated
other
techniques.
Furthermore,
our
paper
underscores
crucial
role
providing
insights
into
human-specific
neurodevelopmental
processes
neurological
disorders,
addressing
scarcity
tissue
translational
neuroscience.
Ultimately,
envision
using
multimodal
longitudinal
propelling
advancements
understanding
neurodevelopment
related
disorders.
Brain,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 2, 2024
Abstract
Neurodevelopmental
disorders
(NDD)
encompass
a
range
of
conditions
marked
by
abnormal
brain
development
in
conjunction
with
impaired
cognitive,
emotional
and
behavioural
functions.
Transgenic
animal
models,
mainly
rodents,
traditionally
served
as
key
tools
for
deciphering
the
molecular
mechanisms
driving
NDD
physiopathology
significantly
contributed
to
pharmacological
interventions
aimed
at
treating
these
disorders.
However,
efficacy
treatments
humans
has
proven
be
limited,
due
part
intrinsic
constraint
models
recapitulate
complex
structure
human
but
also
phenotypic
heterogeneity
found
between
affected
individuals.
Significant
advancements
field
induced
pluripotent
stem
cells
(iPSCs)
offer
promising
avenue
overcoming
challenges.
Indeed,
advanced
differentiation
protocols
generating
iPSC-derived
organoids
gives
an
unprecedented
opportunity
explore
neurodevelopment.
This
review
provides
overview
how
3D
have
been
used
investigate
various
(i.e.
Fragile
X
syndrome,
Rett
Angelman
microlissencephaly,
Prader-Willi
Timothy
tuberous
sclerosis
syndrome)
elucidate
their
pathophysiology.
We
discuss
benefits
limitations
employing
such
innovative
compared
2D
cell
culture
systems
realm
personalized
medicine.
Medical Research Archives,
Journal Year:
2024,
Volume and Issue:
12(2)
Published: Jan. 1, 2024
Developing
drugs
for
brain
disorders
poses
significant
hurdles.
These
challenges
stem
from
the
scarcity
of
optimal
models
preclinical
drug
testing
and
often
observed
lack
translation
to
human
clinical
trials.
Further
complexity
arises
specific
targeting
required
in
many
disorders,
with
delivery
impeded
by
necessity
cross
blood-brain
barrier
(BBB).
As
such,
search
novel
efficient
platforms
development
is
a
vibrant
area
research.
In
acknowledgment
limitations
animal
tests
-
such
as
owing
species
differences
alignment
principles
reduction,
refinement,
replacement
(3Rs),
scientific
community
moving
towards
promoting
animal-free
plans.
this
context,
organoids
are
rapidly
emerging
potential
alternatives
traditional
methods.
early-stage
vitro
models,
mirroring
vivo
complexities,
hold
great
promise
disorders.
Stable
organoid
phenotypes
uncovering
disease-specific
features
could
soon
elevate
them
valuable
strategy
pharmaceutical
range
Recent
advancements
assay-ready
microfluidic
chips
present
considerable
application
development.
This
commentary
briefly
discusses
generation
their
existing
examples,
focusing
on
use
migraine,
prevalent,
complex,
disabling
disorder.
The
associated
opportunities
will
also
be
outlined.
