Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies
Journal of Neural Transmission,
Год журнала:
2024,
Номер
131(5), С. 525 - 561
Опубликована: Март 30, 2024
Язык: Английский
Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking
Translational Psychiatry,
Год журнала:
2023,
Номер
13(1)
Опубликована: Ноя. 27, 2023
The
underlying
genetic
and
epigenetic
mechanisms
driving
functional
adaptations
in
neuronal
excitability
excessive
alcohol
intake
are
poorly
understood.
Small-conductance
Ca
Язык: Английский
DNA methylation of miR-181a-5p mediated by DNMT3b drives renal interstitial fibrosis developed from acute kidney injury
Epigenomics,
Год журнала:
2024,
Номер
16(13), С. 945 - 960
Опубликована: Июль 2, 2024
Aim:
To
explore
the
role
of
miR-181a-5p
in
progression
acute
kidney
injury
(AKI)
to
renal
interstitial
fibrosis
(RIF)
from
perspective
DNA
methylation.
Materials
&
methods:
The
was
confirmed
by
collecting
clinical
samples,
injecting
agomir
into
tail
vein,
and
transfecting
mimic
vitro.
mechanism
miR-181a-5p's
influence
on
AKI
induced
RIF
investigated
methylation-specific
PCR,
bioinformatic
analysis,
transcriptome
sequencing
so
on.
Results:
MiR-181a-5p
plays
an
important
RIF.
DNMT3b-mediated
promoter
hypermethylation
is
main
reason
for
downregulation
miR-181a-5p.
HDAC9
SNAI2
are
direct
targets
Conclusion:
Hypermethylation
mediated
DNMT3b
promotes
targeting
SNAI2.
Язык: Английский
The Impact of Alcohol-Induced Epigenetic Modifications in the Treatment of Alcohol use Disorders
Current Medicinal Chemistry,
Год журнала:
2023,
Номер
31(36), С. 5837 - 5855
Опубликована: Окт. 13, 2023
Alcohol
use
disorders
are
responsible
for
5.9%
of
all
death
annually
and
5.1%
the
global
disease
burden.
It
has
been
suggested
that
alcohol
abuse
can
modify
gene
expression
through
epigenetic
processes,
namely
DNA
histone
methylation,
acetylation,
microRNA
expression.
The
influence
on
mechanisms
leads
to
molecular
adaptation
a
wide
number
brain
circuits,
including
hypothalamus-hypophysis-adrenal
axis,
prefrontal
cortex,
mesolimbic-dopamine
pathways
endogenous
opioid
pathways.
Epigenetic
regulation
represents
an
important
level
alcohol-induced
in
brain.
demonstrated
acute
chronic
exposure
induce
opposite
modifications
mechanisms:
increases
decreases
methylation
inhibits
methyltransferase
activity,
while
induces
hypermethylation
DNA.
Some
studies
investigated
chromatin
status
during
withdrawal
period
craving
showed
was
associated
with
low
status,
elevated
activity
deacetylase
decreased
acetylation.
Given
effects
exerted
by
ethanol
consumption
mechanisms,
structure
modifiers,
such
as
inhibitors
inhibitors,
might
represent
new
potential
strategy
treat
disorder.
Further
investigations
induced
be
helpful
develop
therapies
alcoholism
drug
addiction
targeting
processes.
Язык: Английский
Adolescent social housing protects against adult emotional and cognitive deficits and alters the PFC and NAc transcriptome in male and female C57BL/6J mice
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Дек. 7, 2023
Introduction
Adolescence
is
a
critical
period
in
cognitive
and
emotional
development,
characterized
by
high
levels
of
social
interaction
increases
risk-taking
behavior
including
binge
drinking.
Adolescent
exposure
to
stress
ethanol
have
individually
been
associated
with
the
development
social,
emotional,
deficits,
as
well
increased
risk
for
alcohol
use
disorder.
Disruption
cortical
early
life
and/or
drinking
may
partly
underlie
these
enduring
cognitive,
behavioral
effects.
The
study
goal
implement
novel
neighbor
housing
environment
identify
effects
adolescent
on
(1)
battery
tasks
(2)
adult
behavior,
(3)
nucleus
accumbens
prefrontal
cortex
transcriptome.
Methods
male
female
C57BL/6J
mice
were
single
or
housed
without
access
intermittent
ethanol.
One
cohort
underwent
testing
during
adulthood
determine
preference,
expression
anxiety-like
performance,
patterns
intake.
second
was
sacrificed
late
adolescence
brain
tissue
used
transcriptomics
analysis.
Results
As
adults,
displayed
decreased
interaction,
deficits
object
recognition
task,
relative
neighbor-housed
mice.
There
no
effect
condition
consumption.
did
not
alter
Transcriptomics
analysis
revealed
that
resulted
differential
genes
related
synaptic
plasticity
methylation,
extracellular
matrix
inflammation
cortex.
Discussion
results
indicate
via
model
protect
against
deficits.
In
addition,
suggest
alterations
be
mediated
part
dysregulation
transcription
frontal
accumbens.
Язык: Английский
Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking.
Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Сен. 15, 2023
The
underlying
genetic
and
epigenetic
mechanisms
driving
functional
adaptations
in
neuronal
excitability
excessive
alcohol
intake
are
poorly
understood.
Small-conductance
Ca2+-activated
K+
(KCa2
or
SK)
channels
encoded
by
the
KCNN
family
of
genes
have
emerged
from
preclinical
studies
as
a
key
contributor
to
alcohol-induced
neuroadaptations
alcohol-drinking
monkeys
dependent
mice.
Here,
this
cross-species
analysis
focused
on
KCNN3
DNA
methylation,
gene
expression,
single
nucleotide
polymorphisms
including
alternative
promoters
that
could
influence
surface
trafficking
function
KCa2
channels.
Bisulfite
sequencing
nucleus
accumbens
tissue
mice
revealed
differentially
methylated
region
exon
1A
overlaps
with
predicted
promoter
sequence.
hypermethylation
paralleled
an
increase
expression
transcripts
encode
apamin-insensitive
dominant-negative
channel
isoforms.
A
polymorphic
repeat
macaque
1
did
not
correlate
drinking.
At
protein
level,
KCa2.3
was
significantly
reduced
very
heavy
drinking
monkeys.
Together,
our
findings
dysregulation
represent
complex
mechanism
utilizes
impact
firing
neurons.
Thus,
these
results
provide
support
for
possible
molecular
harmful
use
disorder.
Язык: Английский