Alcoholism Clinical and Experimental Research,
Journal Year:
2018,
Volume and Issue:
42(4), P. 706 - 717
Published: Jan. 16, 2018
Adolescent
intermittent
ethanol
(AIE)
exposure
produces
persistent
impairments
in
cholinergic
and
epigenetic
signaling
alters
markers
of
synapses
the
hippocampal
formation,
effects
that
are
thought
to
drive
dysfunction
adult
rodents.
Donepezil
(Aricept),
a
cholinesterase
inhibitor,
is
used
clinically
ameliorate
memory-related
cognitive
deficits.
Given
donepezil
also
prevents
morphological
impairment
preclinical
models
neuropsychiatric
disorders,
we
investigated
ability
reverse
adaptations
hippocampus
rats
exposed
AIE.
Because
known
relationship
between
dendritic
spine
density
morphology
with
fragile
X
mental
retardation
1
(Fmr1)
gene,
assessed
Fmr1
expression
its
regulation
after
AIE
pretreatment.Adolescent
were
administered
for
16
days
starting
on
postnatal
day
30.
Rats
treated
(2.5
mg/kg)
once
4
20
completion
exposure.
Brains
dissected
out
fourth
dose,
analysis
was
completed
dentate
gyrus
granule
neurons.
A
separate
cohort
rats,
identically,
molecular
studies.AIE
significantly
reduced
altered
characteristics
subclasses
spines.
increased
mRNA
levels
H3-K27
acetylation
occupancy
gene
hippocampus.
Treatment
AIE-exposed
reversed
both
modifications
Fmr1.These
findings
indicate
long-lasting
decreases
changes
suggesting
mechanisms
underlying
previously
reported
behavioral
deficits
The
reversal
these
by
subchronic,
post-AIE
treatment
indicates
can
be
up-regulating
function.
Alcoholism Clinical and Experimental Research,
Journal Year:
2019,
Volume and Issue:
43(9), P. 1806 - 1822
Published: July 23, 2019
The
Neurobiology
of
Adolescent
Drinking
in
Adulthood
(NADIA)
Consortium
has
focused
on
the
impact
adolescent
binge
drinking
brain
development,
particularly
effects
that
persist
into
adulthood.
is
common,
and
while
many
factors
contribute
to
human
development
alcohol
use
during
adolescence,
animal
models
are
critical
for
understanding
specific
consequences
exposure
this
developmental
period
underlying
mechanisms.
Using
intermittent
ethanol
(AIE)
models,
NADIA
investigators
identified
long‐lasting
AIE‐induced
changes
adult
behavior
consistent
with
observations
humans,
such
as
increased
drinking,
anxiety
(particularly
social
anxiety),
impulsivity,
reduced
behavioral
flexibility,
impaired
memory,
disrupted
sleep,
altered
responses
alcohol.
These
associated
multiple
molecular,
cellular,
physiological
alterations
long
after
AIE
exposure.
At
molecular
level,
results
neuroimmune/trophic
factor
balance
epigenetic–microRNA
(miRNA)
signaling
across
glia
neurons.
cellular
history
adulthood
expression
cholinergic,
serotonergic,
dopaminergic
neuron
markers,
attenuated
cortical
thickness,
decreased
neurogenesis,
dendritic
spine
glial
morphology.
This
constellation
adaptations
likely
contributes
observed
neurophysiology,
measured
by
synaptic
physiology,
EEG
patterns,
functional
connectivity.
Many
these
replicate
findings
seen
postmortem
brains
humans
disorder
(AUD).
researchers
now
elucidating
mechanisms
adaptations.
Emerging
data
demonstrate
exercise,
antiinflammatory
drugs,
anticholinesterases,
histone
deacetylase
inhibitors,
other
pharmacological
compounds
able
prevent
(administered
AIE)
and/or
reverse
(given
pathology
studies
support
hypotheses
increases
risk
hazardous
influences
may
provide
insight
novel
therapeutic
targets
neuropathology
AUDs.
Addiction Biology,
Journal Year:
2019,
Volume and Issue:
25(2)
Published: Feb. 18, 2019
Abstract
Binge
drinking
and
alcohol
abuse
are
common
during
adolescence
cause
lasting
pathology.
Preclinical
rodent
studies
using
the
adolescent
intermittent
ethanol
(AIE;
5.0
g/kg,
i.g.,
2‐day
on/2‐day
off
from
postnatal
day
[P]25
to
P55)
model
of
human
binge
report
decreased
basal
forebrain
cholinergic
(ie,
ChAT+)
neurons
that
persist
into
adulthood
P56‐P220).
Recent
link
AIE‐induced
neuroimmune
activation
pathology,
but
underlying
molecular
mechanisms
contributing
persistent
loss
ChAT+
unknown.
We
here
neuron
markers
ChAT,
TrkA,
p75
NTR
),
shrinkage,
increased
expression
marker
pNF‐κB
p65
restored
by
exercise
exposure
P56
P95
after
AIE.
Our
data
reveal
persistently
reduced
following
AIE
is
because
phenotype
most
likely
through
an
epigenetic
mechanism
involving
DNA
methylation
histone
3
lysine
9
dimethylation
(H3K9me2).
Adolescent
caused
a
increase
in
adult
H3K9me2
at
promoter
regions
Chat
Trka
,
which
was
wheel
running.
Exercise
also
reversal
learning
deficits
on
Morris
water
maze.
Together,
these
suggest
signaling
cognitive
linked
suppression
gene
can
be
exercise.
restoration
phenotypic
via
modifications
novel
neuroplasticity.
