Journal of Neuroscience,
Год журнала:
2013,
Номер
33(50), С. 19534 - 19554
Опубликована: Дек. 11, 2013
Adverse
early-life
experiences,
such
as
poor
maternal
care,
program
an
abnormal
stress
response
that
may
involve
altered
balance
between
excitatory
and
inhibitory
signals.
Here,
we
explored
how
(ELS)
affects
transmission
in
corticotrophin-releasing
factor
(CRF)-expressing
dorsal-medial
(mpd)
neurons
of
the
neonatal
mouse
hypothalamus.
We
report
ELS
associates
with
enhanced
glutamatergic
is
manifested
increased
frequency
synaptic
events
extrasynaptic
conductance,
latter
associated
dysfunctional
astrocytic
regulation
glutamate
levels.
The
neurosteroid
5α-pregnan-3α-ol-20-one
(5α3α-THPROG)
endogenous,
positive
modulator
GABA
A
receptors
(GABA
Rs)
abundant
during
brain
development
rises
rapidly
acute
stress,
thereby
enhancing
inhibition
to
curtail
stress-induced
activation
hypothalamic-pituitary-adrenocortical
axis.
In
control
mpd
neurons,
5α3α-THPROG
potently
suppressed
neuronal
discharge,
but
this
action
was
greatly
compromised
by
prior
exposure.
This
insensitivity
did
not
primarily
result
from
perturbations
GABAergic
inhibition,
rather
arose
functionally
drive
onto
neurons.
Previous
reports
indicated
mice
(dams)
lacking
R
δ
subunit
(δ
0/0
)
exhibit
behavior.
Intriguingly,
offspring
showed
some
hallmarks
care
were
further
exacerbated
ELS.
Moreover,
common
ELS,
pups
exhibited
consequently
a
blunted
suppression
firing.
study
reveals
tonic
be
maladaptation
leading
excitation
CRF-releasing
identifies
neurosteroids
putative
early
regulators
neurocircuitry.
Journal of Neuroscience,
Год журнала:
2013,
Номер
33(21), С. 9003 - 9012
Опубликована: Май 22, 2013
Neuropsychiatric
disease
frequently
presents
with
an
underlying
hyporeactivity
or
hyperreactivity
of
the
HPA
stress
axis,
suggesting
exceptional
vulnerability
this
circuitry
to
external
perturbations.
Parental
lifetime
exposures
environmental
challenges
are
associated
increased
offspring
neuropsychiatric
risk,
and
likely
contribute
dysregulation.
While
maternal
influences
have
been
extensively
examined,
much
less
is
known
regarding
specific
role
paternal
factors.
To
investigate
potential
mechanisms
by
which
may
hypothalamic–pituitary–adrenal
(HPA)
axis
dysregulation,
we
exposed
mice
6
weeks
chronic
before
breeding.
As
epidemiological
studies
support
variation
in
germ
cell
susceptibility
reprogramming
across
lifespan,
male
exposure
occurred
either
throughout
puberty
adulthood.
Remarkably,
sires
from
both
groups
displayed
significantly
reduced
responsivity.
Gene
set
enrichment
analyses
regulating
brain
regions,
paraventricular
nucleus
(PVN)
bed
stria
terminalis,
revealed
global
pattern
changes
transcription
suggestive
epigenetic
consistent
altered
responsivity,
including
expression
glucocorticoid-responsive
genes
PVN.
In
examining
transmission,
found
robust
sperm
microRNA
(miR)
content,
where
nine
miRs
were
groups.
Overall,
these
results
demonstrate
that
experience
lifespan
can
induce
impact
regulation,
therefore
offer
novel
insight
into
factors
influencing
risk.
Frontiers in Behavioral Neuroscience,
Год журнала:
2013,
Номер
7
Опубликована: Янв. 1, 2013
Resilience
is
the
ability
to
adapt
successfully
in
face
of
stress
and
adversity.
Stressful
life
events,
trauma,
chronic
adversity
can
have
a
substantial
impact
on
brain
function
structure,
result
development
posttraumatic
disorder
(PTSD),
depression
other
psychiatric
disorders.
However,
most
individuals
do
not
develop
such
illnesses
after
experiencing
stressful
are
thus
thought
be
resilient.
as
successful
adaptation
relies
effective
responses
environmental
challenges
ultimate
resistance
deleterious
effects
stress,
therefore
greater
understanding
factors
that
promote
great
relevance.
This
review
focuses
recent
findings
regarding
genetic,
epigenetic,
developmental,
psychosocial,
neurochemical
considered
essential
contributors
resilience.
Neural
circuits
pathways
involved
mediating
resilience
also
discussed.
The
growing
will
hopefully
lead
new
pharmacological
psychological
interventions
for
enhancing
mitigating
untoward
consequences.
Behavioral and Brain Sciences,
Год журнала:
2014,
Номер
38
Опубликована: Авг. 27, 2014
Abstract
The
well-replicated
observation
that
many
people
maintain
mental
health
despite
exposure
to
severe
psychological
or
physical
adversity
has
ignited
interest
in
the
mechanisms
protect
against
stress-related
illness.
Focusing
on
resilience
rather
than
pathophysiology
ways
represents
a
paradigm
shift
clinical-psychological
and
psychiatric
research
great
potential
for
development
of
new
prevention
treatment
strategies.
More
recently,
into
also
arrived
neurobiological
community,
posing
nontrivial
questions
about
ecological
validity
translatability.
Drawing
concepts
findings
from
transdiagnostic
psychiatry,
emotion
research,
behavioral
cognitive
neuroscience,
we
propose
unified
theoretical
framework
neuroscientific
study
general
mechanisms.
is
applicable
both
animal
human
supports
design
interpretation
translational
studies.
theory
emphasizes
causal
role
stimulus
appraisal
(evaluation)
processes
generation
emotional
responses,
including
responses
stressors.
On
this
basis,
it
posits
positive
(non-negative)
style
key
mechanism
protects
detrimental
effects
stress
mediates
other
known
factors.
Appraisal
shaped
by
three
classes
–
situation
classification,
reappraisal,
interference
inhibition
can
be
investigated
at
neural
level.
Prospects
future
are
discussed.
Science,
Год журнала:
2013,
Номер
339(6123), С. 1095 - 1099
Опубликована: Фев. 28, 2013
Prenatal
infection
and
exposure
to
traumatizing
experiences
during
peripuberty
have
each
been
associated
with
increased
risk
for
neuropsychiatric
disorders.
Evidence
is
lacking
the
cumulative
impact
of
such
prenatal
postnatal
environmental
challenges
on
brain
functions
vulnerability
psychiatric
disease.
Here,
we
show
in
a
translational
mouse
model
that
combined
immune
challenge
peripubertal
stress
induces
synergistic
pathological
effects
adult
behavioral
neurochemistry.
We
further
demonstrate
insult
markedly
increases
pubescent
offspring
changes
response
stress.
Our
findings
reveal
interactions
between
two
adverse
factors
individually
disease
support
theories
mental
illnesses
delayed
onsets
involve
multiple
hits.
Proceedings of the National Academy of Sciences,
Год журнала:
2018,
Номер
115(40), С. 10154 - 10159
Опубликована: Сен. 24, 2018
The
hippocampus
plays
key
roles
in
cognition
and
affect
serves
as
a
model
system
for
structure/function
studies
animals.
So
far,
its
complex
anatomy
has
challenged
investigations
targeting
substructural
organization
humans.
State-of-the-art
MRI
offers
the
resolution
versatility
to
identify
hippocampal
subfields,
assess
microstructure,
study
topographical
principles
of
connectivity
vivo.
We
developed
an
approach
unfold
human
examine
spatial
variations
intrinsic
functional
large
cohort
healthy
adults.
In
addition
mapping
common
unique
connections
across
we
identified
two
main
axes
subregional
transitions.
An
anterior/posterior
gradient
followed
long-axis
landmarks
metaanalytical
findings
from
task-based
MRI,
while
medial/lateral
infolding
correlated
with
proxies
cortical
myelin.
Findings
were
consistent
independent
sample
highly
stable
resting-state
scans.
Our
results
provide
robust
evidence
specialization
resting
suggest
intriguing
interplay
between
microstructure.
