medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 31, 2023
Pituitary
adenylate
cyclase-activating
polypeptide
(PACAP)
regulates
plasticity
in
brain
systems
underlying
arousal
and
memory
is
associated
with
posttraumatic
stress
disorder
(PTSD).
Research
animal
models
suggests
that
PACAP
modulates
entorhinal
cortex
(EC)
input
to
the
hippocampus,
contributing
impaired
contextual
fear
conditioning.
In
PTSD,
higher
activity
of
amygdala
threat
stimuli
lower
functional
connectivity
hippocampus.
However,
PACAP-affiliated
structural
alterations
these
regions
have
not
been
reported.
Here,
we
examined
whether
peripheral
levels
were
neuronal
morphology
hippocampus
(primary
analysis),
EC
(secondary
analysis)
using
Neurite
Orientation
Dispersion
Density
Imaging.
Frontiers in Psychiatry,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 27, 2025
Stress
is
necessary
for
survival.
However,
chronic
unnecessary
stress
exposure
leads
to
cardiovascular,
gastrointestinal
and
neuropsychiatric
disorders.
Thus,
understanding
the
mechanisms
involved
in
initiation
maintenance
of
response
essential
since
it
may
reveal
underpinning
pathophysiology
these
disorders
aid
development
medication
treat
stress-mediated
diseases.
Pituitary
adenylyl
cyclase
activating
polypeptide
(PACAP)
its
receptors
(PAC1,
VPAC1
VPAC2)
are
expressed
hypothalamus
other
brain
areas
as
well
adrenal
gland.
Previous
research
has
shown
that
this
peptide/receptor
system
serves
a
modulator
response.
In
addition
modulating
response,
also
be
connected
emerging
role
neuroprotective
against
hypoxia,
ischemia,
neurodegeneration.
This
article
aims
review
literature
regarding
PACAP
involvement
different
regions
microglia
PACAP-mediated
modulation
long-term
adaptation
recognizable
clinically
survival
with
resilience
while
manifested
anxiety,
depression
neurobehavioral
Molecular Psychiatry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 31, 2025
Most
of
the
fear
literature
on
humans
and
animals
tests
healthy
individuals.
However,
memories
can
differ
between
individuals
those
previously
exposed
to
traumatic
stress,
such
as
a
car
accident,
sexual
abuse,
military
combat
personal
assault.
Traumatic
stress
lead
post-traumatic
disorder
(PTSD)
which
presents
alterations
in
memories,
an
impairment
extinction
recall.
PTSD-like
animal
models
are
single
highly
stressful
experience
laboratory,
immobilization
or
single-prolonged
stress.
Some
days
later,
model
be
tested
procedures
that
help
uncover
molecular
mechanisms
memories.
In
this
review,
there
discussed
stress-induced
patients
with
PTSD
models.
The
focus
is
effects
estradiol
cortisol/corticosterone
hormones
different
genes,
FKBP
prolyl
isomerase
5
gene
(FKBP5)
-
FK506
binding
protein
51
(FKBP51),
pituitary
adenylate
cyclase-activating
peptide
(PACAP)
polypeptide
type
I
receptor
(PAC1R),
endocannabinoid
(eCB)
system
tropomyosin
kinase
B
(TrkB)
brain-derived
neurotrophic
factor
(BDNF).
conclusion
greater
emphasis
should
placed
investigating
PTSD,
through
direct
testing
use
relevant
Frontiers in Neuroscience,
Год журнала:
2025,
Номер
19
Опубликована: Фев. 5, 2025
The
neuropeptide
pituitary
adenylate
cyclase-activating
peptide
(PACAP)
plays
a
pivotal
role
in
regulating
stress,
fear,
and
anxiety
responses.
Genetic
molecular
studies
investigating
PACAP
demonstrate
sex-dimorphic
characteristics,
with
females
exhibiting
increased
reactivity
of
signaling
neuropsychiatric
disorders.
Studies
expand
the
to
substance
use
disorders
(SUD)
by
demonstrating
modulation
can
lead
neurobiological
changes
induced
nicotine,
ethanol,
stimulants
opioids.
Given
that
SUD
exhibit
distinct
drug
use,
relapse,
withdrawal
sensitivity
relative
males,
we
hypothesize
system
contributes
these
sex-specific
differences.
Therefore,
review
characterizing
at
molecular,
brain
regional,
behavioral
levels
relevant
addiction
cycle.
We
present
literature
linking
disorders,
which
intricate
within
neuronal
pathways
modulating
addiction.
are
more
particularly
susceptible
PACAP-related
during
intoxication
phases
Altogether
understanding
differences
offers
foundation
for
future
aimed
developing
tailored
interventions
addressing
SUD.
European journal of psychotraumatology,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 8, 2024
Pituitary
adenylate
cyclase-activating
polypeptide
(PACAP)
regulates
plasticity
in
brain
systems
underlying
arousal
and
memory
is
associated
with
posttraumatic
stress
disorder
(PTSD).
Research
animal
models
suggests
that
PACAP
modulates
entorhinal
cortex
(EC)
input
to
the
hippocampus,
contributing
impaired
contextual
fear
conditioning.
In
PTSD,
higher
activity
of
amygdala
threat
stimuli
lower
functional
connectivity
hippocampus.
However,
PACAP-affiliated
structural
alterations
these
regions
have
not
been
investigated
PTSD.
Here,
we
examined
whether
peripheral
levels
were
neuronal
morphology
hippocampus
(primary
analyses),
EC
(secondary)
using
Neurite
Orientation
Dispersion
Density
Imaging.
eNeuro,
Год журнала:
2023,
Номер
10(12), С. ENEURO.0424 - 23.2023
Опубликована: Дек. 1, 2023
Abstract
Alcohol
use
disorder
(AUD)
is
a
complex
psychiatric
disease
characterized
by
periods
of
heavy
drinking
and
withdrawal.
Chronic
exposure
to
ethanol
causes
profound
neuroadaptations
in
the
extended
amygdala,
which
cause
allostatic
changes
promoting
excessive
drinking.
The
bed
nucleus
stria
terminalis
(BNST),
brain
region
involved
both
anxiety-like
behavior,
shows
particularly
high
levels
pituitary
adenylate
cyclase-activating
polypeptide
(PACAP),
key
mediator
stress
response.
Recently,
role
for
PACAP
withdrawal-induced
alcohol
behavior
alcohol-dependent
rats
has
been
proposed;
whether
system
BNST
also
recruited
other
models
addiction
it
local
or
nonlocal
origin
currently
unknown.
Here,
we
show
that
immunoreactivity
increased
selectively
C57BL/6J
mice
exposed
chronic,
intermittent
access
ethanol.
While
(PACAP)
type
1
receptor-expressing
cells
were
unchanged
chronic
alcohol,
peptide
closely
related
PACAP,
calcitonin
gene-related
neuropeptide,
found
be
BNST.
Finally,
using
retrograde
chemogenetic
approach
PACAP-ires-Cre
mice,
inhibition
neuronal
afferents
reduced
Our
data
suggest
voluntary
nonlocally
originating
projections
regulate
intake,
indicating
this
may
represent
promising
target
novel
AUD
therapies.
Psychological Medicine,
Год журнала:
2024,
Номер
unknown, С. 1 - 12
Опубликована: Дек. 16, 2024
Abstract
Background
Pediatric
bipolar
disorder
(PBD)
is
characterized
by
abnormal
functional
connectivity
among
distributed
brain
regions.
Increasing
evidence
suggests
a
role
for
the
limbic
network
(LN)
and
triple
model
in
pathophysiology
of
(BD).
However,
specific
relationship
between
LN
PBD
remains
unclear.
This
study
aimed
to
investigate
aberrant
causal
connections
these
four
core
networks
PBD.
Method
Resting-state
MRI
scans
from
92
patients
40
healthy
controls
(HCs)
were
analyzed.
Dynamic
Causal
Modeling
(DCM)
was
employed
assess
effective
(EC)
networks.
Parametric
empirical
Bayes
(PEB)
analysis
conducted
identify
ECs
associated
with
group
differences,
as
well
depression
mania
severity.
Leave-one-out
cross-validation
(LOOCV)
used
test
predictive
accuracy.
Result
Compared
HCs,
exhibited
primarily
excitatory
bottom-up
salience
(SN)
bidirectional
default
mode
(DMN)
SN.
In
PBD,
top-down
individuals
higher
severity
but
inhibitory
those
LOOCV
identified
dysconnectivity
circuits
involving
caudate
hippocampus
being
severity,
respectively.
Conclusions
Disrupted
distinguish
controls,
while
disruptions
relate
mood
state
differences.
These
findings
offer
insight
into
neural
mechanisms
