IEEE Transactions on Neural Systems and Rehabilitation Engineering,
Journal Year:
2024,
Volume and Issue:
32, P. 1314 - 1323
Published: Jan. 1, 2024
Depression
is
one
of
the
most
serious
mental
disorders
affecting
modern
human
life
and
often
caused
by
chronic
stress.
Dopamine
system
dysfunction
proposed
to
contribute
pathophysiology
stress,
especially
ventral
tegmental
area
(VTA)
which
mainly
consists
dopaminergic
neurons.
Focused
ultrasound
stimulation
(FUS)
a
promising
neuromodulation
modality
multiple
studies
have
demonstrated
effective
ultrasonic
activation
cortical,
subcortical,
related
networks.
However,
effects
FUS
on
dopamine
potential
link
stress-induced
depressive
behaviors
are
relatively
unknown.
Here,
we
measured
targeting
VTA
improvement
depression-like
behavior
evaluated
concentration
in
downstream
region
-
medial
prefrontal
cortex
(mPFC).
We
found
that
treatment
alleviated
restraint
stress
(CRS)
-induced
anhedonia
despair
behavior.
Using
an
vivo
photometry
approach,
analyzed
signal
mPFC
revealed
significant
increase
following
FUS,
positively
associated
with
also
protected
neurons
from
damage
CRS
exposure.
Thus,
these
results
significantly
rescued
depressive-like
declined
level
induced
CRS.
These
beneficial
might
be
due
protection
DA
neuron
VTA.
Our
findings
suggest
could
serve
as
new
therapeutic
strategy
for
stress-related
disorders.
Cell Reports,
Journal Year:
2022,
Volume and Issue:
40(8), P. 111246 - 111246
Published: Aug. 1, 2022
Social
behaviors
are
among
the
most
important
motivated
behaviors.
How
dopamine
(DA),
a
"reward"
signal,
releases
during
social
has
been
topic
of
interest
for
decades.
Here,
we
use
genetically
encoded
DA
sensor,
GRAB
Physiological Reviews,
Journal Year:
2024,
Volume and Issue:
104(3), P. 1205 - 1263
Published: March 14, 2024
Stress
resilience
is
the
phenomenon
that
some
people
maintain
their
mental
health
despite
exposure
to
adversity
or
show
only
temporary
impairments
followed
by
quick
recovery.
Resilience
research
attempts
unravel
factors
and
mechanisms
make
possible
harness
its
insights
for
development
of
preventative
interventions
in
individuals
at
risk
acquiring
stress-related
dysfunctions.
Biological
has
been
lagging
behind
psychological
social
sciences
but
seen
a
massive
surge
recent
years.
At
same
time,
progress
this
field
hampered
methodological
challenges
related
finding
suitable
operationalizations
study
designs,
replicating
findings,
modeling
animals.
We
embed
review
behavioral,
neuroimaging,
neurobiological,
systems
biological
findings
adults
critical
methods
discussion.
find
preliminary
evidence
hippocampus-based
pattern
separation
prefrontal-based
cognitive
control
functions
protect
against
pathological
fears
aftermath
singular,
event-type
stressors
[as
found
fear-related
disorders,
including
simpler
forms
posttraumatic
stress
disorder
(PTSD)]
facilitating
perception
safety.
Reward
system-based
pursuit
savoring
positive
reinforcers
appear
more
generalized
dysfunctions
anxious-depressive
spectrum
resulting
from
severe
longer-lasting
(as
depression,
comorbid
anxiety,
PTSD).
Links
between
preserved
functioning
these
neural
under
neuroplasticity,
immunoregulation,
gut
microbiome
composition,
integrity
barrier
blood-brain
are
beginning
emerge.
On
basis,
avenues
pointed
out.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Jan. 2, 2025
Protein/protein
interactions
(PPI)
play
crucial
roles
in
neuronal
functions.
Yet,
their
potential
as
drug
targets
for
brain
disorders
remains
underexplored.
The
fibroblast
growth
factor
14
(FGF14)/voltage-gated
Na+
channel
1.6
(Nav1.6)
complex
regulates
excitability
of
medium
spiny
neurons
(MSN)
the
nucleus
accumbens
(NAc),
a
central
hub
reward
circuitry
that
controls
motivated
behaviors.
Here,
we
identified
compound
1028
(IUPAC:
ethyl
3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate),
brain-permeable
small
molecule
FGF14R117,
critical
residue
located
within
druggable
pocket
at
FGF14/Nav1.6
PPI
interface.
We
found
modulates
assembly
and
depolarizes
voltage-dependence
Nav1.6
inactivation
with
nanomolar
potency
by
modulating
intramolecular
interaction
between
III-IV
linker
C-terminal
domain
channel.
Consistent
compound's
effects
on
inactivation,
enhances
MSN
ex
vivo
accumbal
neuron
firing
rate
murine
models.
Systemic
administration
maintains
behavioral
motivation
preferentially
during
motivationally
deficient
conditions
These
were
abrogated
gene
silencing
Fgf14
NAc
accompanied
selective
reduction
dopamine
levels
consumption
findings
underscore
to
selectively
regulate
behaviors
associated
neuropsychiatric
through
targeting
PPIs
neurons.
interfaces
have
emerged
develop
medications
less
side
effects.
Dvorak
et
al.
show
is
an
approach
psychiatric
discovery.
