Neurobiology of Stress,
Год журнала:
2022,
Номер
20, С. 100484 - 100484
Опубликована: Сен. 1, 2022
Early
life
adversity
(ELA)
is
a
major
risk
factor
for
the
development
of
pathology,
including
anxiety
disorders.
Neurodevelopmental
and
behavioral
outcomes
following
ELA
are
multifaceted
influenced
heavily
by
type
experienced
sex
individual
experiencing
ELA.
It
remains
unclear
what
properties
portend
differential
neurobiological
basis
sex-differences
negative
outcomes.
Predictability
postnatal
environment
has
emerged
as
being
core
feature
supporting
development,
with
most
salient
signals
deriving
from
parental
care.
care
may
be
distinguishing
different
forms
ELA,
degree
predictability
afforded
these
manipulations
contribute
to
diversity
observed
across
models.
Further,
questions
remain
whether
differing
levels
effects
on
neurodevelopment
expression
genes
associated
pathology.
Here,
we
tested
hypothesis
that
changes
in
maternal
behavior
mice
would
contingent
experienced,
directly
comparing
limited
bedding
nesting
(LBN)
separation
(MS)
paradigms.
We
then
altered
corticotropin-releasing
hormone
(Crh),
sexually-dimorphic
neuropeptide
regulates
threat-related
learning,
amygdala
male
female
mice.
The
LBN
manipulation
reliably
increased
entropy
care,
measure
indicates
lower
between
sequences
dam
behavior.
MS
rearing
similarly
frequency
nest
sorties
licking
pups
but
had
mixed
other
aspects
dam-,
pup-,
nest-related
behaviors.
Increased
Crh-related
was
gene
measures
showing
significant
interaction
manipulation.
Specifically,
males,
not
females,
primarily
males.
present
study
provides
evidence
models
demonstrates
robust
consequences
experience
critically
stress
responding
differences
European Journal of Neuroscience,
Год журнала:
2021,
Номер
55(9-10), С. 2170 - 2195
Опубликована: Апрель 7, 2021
Addiction
is
a
chronic
relapsing
disorder
with
devastating
personal,
societal,
and
economic
consequences.
In
humans,
early-life
adversity
(ELA)
such
as
trauma,
neglect,
resource
scarcity
are
linked
increased
risk
of
later-life
addiction,
but
the
brain
mechanisms
underlying
this
link
still
poorly
understood.
Here,
we
focus
on
data
from
rodent
models
ELA
in
which
causal
effects
responses
to
drugs
neurodevelopmental
by
increases
vulnerability
addiction
can
be
determined.
We
first
summarize
evidence
for
between
then
describe
how
commonly
modeled
rodents.
Since
heterogeneous
disease
many
individually
varying
behavioral
aspects
that
may
impacted
ELA,
next
discuss
common
assays
addiction-like
behaviors.
specific
addiction-relevant
phenotypes
caused
male
female
rodents
some
changes
reward
stress
circuits
likely
responsible.
By
better
understanding
neural
promotes
vulnerability,
hope
facilitate
development
new
approaches
preventing
or
treating
those
history
ELA.
Translational Psychiatry,
Год журнала:
2022,
Номер
12(1)
Опубликована: Июнь 16, 2022
Abstract
In
humans,
early-life
adversity
(ELA)
such
as
trauma,
poverty,
and
chaotic
environment
is
linked
to
increased
risk
of
later-life
emotional
disorders
including
depression
substance
abuse.
These
involve
underlying
disruption
reward
circuits
likely
vary
by
sex.
Accordingly,
we
previously
found
that
ELA
leads
anhedonia
for
natural
rewards
cocaine
in
male
rodents,
whereas
females
instead
increases
vulnerability
addiction-like
use
opioid
drugs
palatable
food.
While
these
findings
suggest
ELA-induced
circuitry
may
differ
between
the
sexes,
specific
circuit
nodes
are
influenced
either
sex
remain
poorly
understood.
Here,
adult
Sprague-Dawley
rats,
ask
how
impacts
addiction-relevant
behaviors
tested
after
females.
We
probe
potential
mechanisms
males
assessing
opioid-associated
neuronal
activation
stress
nucleus
accumbens
(NAc),
amygdala,
medial
prefrontal
cortex
(mPFC),
paraventricular
thalamus.
find
diminishes
opioid-seeking
males,
alters
heroin-induced
NAc,
PFC,
suggesting
a
circuit-based
mechanism.
studies
demonstrate
behavioral
neurobiological
disruptions
consistent
with
unlike
seeking
saw
Our
findings,
taken
together
our
prior
work,
men
women
could
face
qualitatively
different
mental
health
consequences
ELA,
which
be
essential
individually
tailoring
future
intervention
strategies.
Frontiers in Systems Neuroscience,
Год журнала:
2022,
Номер
16
Опубликована: Июнь 23, 2022
It
is
now
well-established
that
early
life
adversity
(ELA)
predisposes
individuals
to
develop
several
neuropsychiatric
conditions,
including
anxiety
disorders,
and
major
depressive
disorder.
However,
ELA
a
very
broad
term,
encompassing
multiple
types
of
negative
childhood
experiences,
physical,
sexual
emotional
abuse,
physical
neglect,
as
well
trauma
associated
with
chronic
illness,
family
separation,
natural
disasters,
accidents,
witnessing
violent
crime.
Emerging
literature
suggests
in
humans,
different
adverse
experiences
are
more
or
less
likely
produce
susceptibilities
certain
conditions
involve
affective
dysfunction.
To
investigate
the
driving
mechanisms
underlying
connection
between
experience
subsequent
disease,
neuroscientists
have
developed
rodent
models
ELA,
pain
exposure,
maternal
deprivation,
limited
resources.
These
studies
also
shown
paradigms
but
somewhat
overlapping
behavioral
phenotypes.
In
this
review,
we
first
may
be
outcomes
brain
changes
humans.
We
next
evaluate
whether
can
provide
translationally
relevant
information
regarding
links
specific
neural
circuits
Frontiers in Behavioral Neuroscience,
Год журнала:
2020,
Номер
14
Опубликована: Май 27, 2020
Forced
abstinence
(FA)
from
alcohol
has
been
shown
to
produce
a
variety
of
anxiety-
and
depression-like
symptoms
in
animal
models.
Somatostatin
(SST)
neurons,
subtype
GABAergic
neurons
found
throughout
the
brain,
are
novel
neural
target
with
potential
treatment
implications
affective
disorders,
yet
their
role
use
disorders
(AUD)
remains
be
explored.
Here,
we
examined
neuroadaptations
SST
during
forced
voluntary
consumption.
Following
6
weeks
two-bottle
choice
consumption
protracted
abstinence,
male
female
C57BL/6J
mice
exhibited
heightened,
but
sex-specific,
depressive-like
behavioral
profile
sucrose
preference
test
(SPT)
swim
(FST),
without
changes
anxiety-like
behaviors
elevated
plus
maze
(EPM)
open
field
(OFT).
FST-induced
cFos
expressions
prefrontal
cortex
(PFC)
ventral
bed
nucleus
stria
terminalis
(vBNST)
were
altered
FA-exposed
only,
suggesting
sex-specific
effect
on
response
acute
stress.
immunoreactivity
these
regions
was
unaffected
by
while
differences
seen
SST/cFos
co-expression
vBNST.
No
or
lateral
central
amygdala
(CEA)
basolateral
(BLA).
Additionally,
displayed
opposing
alterations
PFC
vBNST,
heightened
intrinsic
excitability
diminished
These
findings
provide
an
overall
framework
abstinence-induced
key
brain
involved
emotional
regulation
processing.
Neurobiology of Stress,
Год журнала:
2021,
Номер
15, С. 100348 - 100348
Опубликована: Май 25, 2021
Alterations
in
the
brain-gut
system
have
been
implicated
various
disease
states,
but
little
is
known
about
how
early-life
adversity
(ELA)
impacts
development
and
adult
health
as
mediated
by
interactions.
We
hypothesize
that
ELA
disrupts
components
of
system,
thereby
increasing
susceptibility
to
disordered
mood.
In
a
sample
128
healthy
participants,
history
current
stress,
depression,
anxiety
were
assessed
using
validated
questionnaires.
Fecal
metabolites
measured
liquid
chromatography
tandem
mass
spectrometry-based
untargeted
metabolomic
profiling.
Functional
brain
connectivity
was
evaluated
magnetic
resonance
imaging.
Sparse
partial
least
squares-discriminant
analysis,
controlling
for
sex,
body
index,
age,
diet
used
predict
alterations
function
ELA.
correlated
with
four
gut-regulated
within
glutamate
pathway
(5-oxoproline,
malate,
urate,
gamma
methyl
ester)
functional
primarily
sensorimotor,
salience,
central
executive
networks.
Integrated
analyses
revealed
significant
associations
between
these
metabolites,
connectivity,
scores
perceived
anxiety,
depression.
This
study
reveals
novel
association
ELA,
axis,
increased
vulnerability
negative
mood
stress.
Results
from
raise
hypothesis
select
may
contribute
adverse
effects
critical
period
stress
on
neural
via
pathways
related
glutamatergic
excitotoxicity
oxidative
Developmental Cognitive Neuroscience,
Год журнала:
2021,
Номер
48, С. 100924 - 100924
Опубликована: Янв. 27, 2021
Adversity
early
in
life
substantially
impacts
prefrontal
cortex
(PFC)
development
and
vulnerability
to
later-life
psychopathology.
Importantly,
repeated
adverse
experiences
throughout
childhood
increase
the
risk
for
PFC-mediated
behavioral
deficits
more
commonly
women.
Evidence
from
animal
models
points
effects
of
adversity
on
neural
dysfunction;
however,
few
studies
have
investigated
neurobiological
underpinnings
sex-specific,
long-term
consequences
multiple
developmental
stressors.
We
modeled
rats
via
maternal
separation
(postnatal
day
(P)2-20)
juvenile
social
isolation
(P21-35).
In
adulthood,
anxiety-like
behavior
was
assessed
elevated
zero
maze
presence
structural
integrity
PFC
perineuronal
nets
(PNNs)
enwrapping
parvalbumin
(PV)-expressing
interneurons
quantified.
PNNs
are
extracellular
matrix
structures
formed
during
critical
periods
postnatal
that
play
a
key
role
plasticity
PV
cells.
observed
female-specific
effect
hyperactivity
risk-assessment
behavior.
Moreover,
females
-
but
not
males
exposed
hits
demonstrated
reduction
cells
adulthood.
also
potentiated
+
PNN
integrity.
These
findings
suggest
sex-specific
impact
neurostructural
implicate
as
contributor
associated
dysfunction.
Frontiers in Neuroscience,
Год журнала:
2022,
Номер
15
Опубликована: Янв. 4, 2022
Early
life
stress
is
thought
to
be
a
risk
factor
for
emotional
disorders,
particularly
depression
and
anxiety.
Although
the
excitation/inhibition
(E/I)
imbalance
has
been
implicated
in
neuropsychiatric
whether
early
affects
E/I
balance
medial
prefrontal
cortex
at
various
developmental
stages
unclear.
In
this
study,
rats
exposed
maternal
separation
(MS)
that
exhibited
well-established
paradigm
were
used
evaluate
adolescence
(postnatal
day
P43-60)
adulthood
(P82-100)
by
behavior
tests,
whole-cell
recordings,
microdialysis
coupled
with
high
performance
liquid
chromatography-mass
spectrometry
(HPLC-MS)
analysis.
First,
behavioral
tests
revealed
MS
induced
both
anxiety-
depressive-like
behaviors
adolescent
but
only
adult
rats.
Second,
increased
action
potential
frequency
of
synaptic
transmission
onto
L5
pyramidal
neurons
prelimbic
(PrL)
brain
region
while
decreasing
Finally,
increases
extracellular
glutamate
levels
decreased
paired-pulse
ratio
evoked
excitatory
postsynaptic
currents
(EPSCs)
PrL
contrast,
EPSCs
The
present
results
reveal
key
role
different
MS-induced
disorders
may
related
altered
probability
presynaptic
release
stages.
Addiction Neuroscience,
Год журнала:
2023,
Номер
6, С. 100067 - 100067
Опубликована: Янв. 26, 2023
In
humans,
exposure
to
early
life
stress
(ELS)
is
an
established
risk
factor
for
the
development
of
substance
use
disorders
(SUDs)
during
later
life.
Similarly,
rodents
exposed
ELS
involving
disrupted
mother-infant
interactions,
such
as
maternal
separation
(MS)
or
adverse
caregiving
due
scarcity-adversity
induced
by
limited
bedding
and
nesting
(LBN)
conditions,
also
exhibit
long-term
alterations
in
alcohol
drug
consumption.
both
humans
rodents,
there
a
range
addiction-related
behaviors
that
are
associated
with
even
predictive
subsequent
SUDs.
these
include
increased
anxiety-like
behavior,
impulsivity,
novelty-seeking,
altered
intake
patterns,
well
reward-related
processes
consummatory
social
behaviors.
Importantly,
expression
often
varies
throughout
lifespan.
Moreover,
preclinical
studies
suggest
sex
differences
play
role
how
impacts
reward
phenotypes
underlying
brain
circuitry.
Here,
addiction-relevant
behavioral
outcomes
mesolimbic
dopamine
(DA)
dysfunction
resulting
from
form
MS
LBN
discussed
focus
on
age-
sex-dependent
effects.
Overall,
findings
may
increase
susceptibility
SUDs
interfering
normal
maturation
function.