Molecular Neurobiology,
Journal Year:
2022,
Volume and Issue:
59(6), P. 3913 - 3932
Published: April 18, 2022
Early
life
stress
(ELS)
is
known
to
modify
trajectories
of
brain
dopaminergic
development,
but
the
mechanisms
underlying
have
not
been
determined.
ELS
perturbs
immune
system
and
microglia
reactivity,
inflammation
influence
transmission
development.
Whether
mediate
effects
on
dopamine
(DA)
development
still
unknown.
We
explored
repeated
early
social
in
male
female
mice
through
histological,
electrophysiological,
transcriptomic
analyses.
Furthermore,
we
tested
whether
these
could
be
mediated
by
ELS-induced
altered
microglia/immune
activity
a
pharmacological
approach.
found
that
DA
neurons
morphology,
reduced
transporter
(DAT)
tyrosine
hydroxylase
expression,
lowered
DAT-mediated
currents
ventral
tegmental
area
substantia
nigra
only.
Notably,
stress-induced
alterations
were
prevented
minocycline,
an
inhibitor
activation.
Transcriptome
analysis
developing
revealed
caused
downregulation
alteration
hormonal
peptide
signaling
pathways.
Results
from
this
study
offer
new
insight
into
response
maturation
after
ELS,
providing
evidence
neuroimmune
interaction,
sex
differences,
regional
specificity.
Neuroscience & Biobehavioral Reviews,
Journal Year:
2019,
Volume and Issue:
108, P. 48 - 77
Published: Oct. 27, 2019
The
ventral
tegmental
area
dopamine
(VTA-DA)
mesolimbic
circuit
processes
emotional,
motivational,
and
social
reward
associations
together
with
their
more
demanding
cognitive
aspects
that
involve
the
mesocortical
circuitry.
Coping
stress
increases
VTA-DA
excitability,
but
when
stressor
becomes
chronic
is
less
active,
which
may
lead
to
degeneration
local
microglial
activation.
This
switch
between
activation
inhibition
of
neurons
modulated
by
e.g.
corticotropin-releasing
hormone
(CRH),
opioids,
brain-derived
neurotrophic
factor
(BDNF),
adrenal
glucocorticoids.
These
actions
are
coordinated
energy-demanding
stress-coping
styles
promote
behavioral
adaptation.
VTA
circuits
show
sexual
dimorphism
programmed
sex
hormones
during
perinatal
life
in
a
manner
can
be
affected
glucocorticoid
exposure.
We
conclude
insight
role
plasticity
connectivity,
processing
stress-coping,
will
helpful
better
understand
mechanism
resilience
breakdown
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.
Journal of Child Psychology and Psychiatry,
Journal Year:
2024,
Volume and Issue:
65(4), P. 538 - 567
Published: March 1, 2024
Depression
is
a
serious
public
health
problem,
and
adolescence
an
‘age
of
risk’
for
the
onset
Major
Depressive
Disorder.
Recently,
we
others
have
proposed
neuroimmune
network
models
that
highlight
bidirectional
communication
between
brain
immune
system
in
both
mental
physical
health,
including
depression.
These
draw
on
research
indicating
cellular
actors
(particularly
monocytes)
signaling
molecules
cytokines)
orchestrate
inflammation
periphery
can
directly
modulate
structure
function
brain.
In
brain,
inflammatory
activity
heightens
sensitivity
to
threats
cortico‐amygdala
circuit,
lowers
rewards
cortico‐striatal
alters
executive
control
emotion
regulation
prefrontal
cortex.
When
dysregulated,
particularly
under
conditions
chronic
stress,
generate
feelings
dysphoria,
distress,
anhedonia.
This
initiate
unhealthy,
self‐medicating
behaviors
(e.g.
substance
use,
poor
diet)
manage
which
further
heighten
inflammation.
Over
time,
dysregulation
these
circuits
response
may
compound
each
other
form
positive
feedback
loop,
whereby
one
organ
exacerbates
other.
We
suggest
this
dynamic
joint
vulnerability
depression,
during
adolescence.
three
goals
present
paper.
First,
extend
developmental
framework
risk
depression
Second,
examine
how
perspective
help
explain
high
rates
comorbidity
psychiatric
disorders
across
development,
multimorbidity
stress‐related
medical
illnesses.
Finally,
consider
identifying
pathways
facilitate
‘next
generation’
behavioral
biological
interventions
target
treat,
ideally
prevent,
youth
adolescents.
Biological Psychiatry,
Journal Year:
2020,
Volume and Issue:
89(2), P. 134 - 143
Published: June 17, 2020
Both
human
and
animal
studies
support
the
relationship
between
depression
reward
processing
abnormalities,
giving
rise
to
expectation
that
neural
signals
of
these
processes
may
serve
as
biomarkers
or
mechanistic
treatment
targets.
Given
great
promise
this
research
line,
we
scrutinized
those
findings
theoretical
claims
underlie
them.
To
achieve
this,
applied
framework
provided
by
classical
work
on
causality
well
contemporary
approaches
prediction.
We
identified
a
number
conceptual,
practical,
analytical
challenges
line
used
preregistered
meta-analysis
quantify
longitudinal
associations
abnormalities
depression.
also
investigated
impact
measurement
error
reported
data.
found
do
not
reach
levels
would
be
useful
for
clinical
prediction,
yet
available
evidence
does
preclude
possible
causal
role
in
