Translational Psychiatry,
Год журнала:
2022,
Номер
12(1)
Опубликована: Фев. 3, 2022
Abstract
Deep
brain
stimulation
(DBS)
of
structures
in
the
brain’s
reward
system
is
a
promising
therapeutic
option
for
patients
with
treatment-resistant
depression
(TRD).
Recently,
DBS
habenula
(HB)
anti-reward
has
also
been
reported
to
alleviate
depressive
symptoms
TRD
or
bipolar
disorder
(BD).
In
this
pilot
open-label
prospective
study,
we
explored
safety
and
clinical
effectiveness
HB–DBS
treatment
seven
BD.
Also,
local
field
potentials
(LFPs)
were
recorded
from
patients’
left
right
HB
explore
power
asymmetry
oscillatory
activities
as
putative
biomarkers
underlying
disease
state.
At
1-month
follow-up
(FU),
anxiety
both
reduced
by
49%
(
n
=
7)
along
substantial
improvements
health
status,
functional
impairment,
quality
life.
Although
dropout
rate
was
high
large
variability
response
existed,
generally
maintained
throughout
study
[56%,
46%,
64%
reduction
61%,
48%,
70%
at
3-month
FU
5),
6-month
12-month
3),
respectively].
After
surgery,
sustained
mania
found
two
who
presented
mild
hypomania
baseline.
Another
patient,
however,
experienced
an
acute
manic
episode
2
months
after
surgery
that
required
hospitalization.
Additionally,
weaker
more
symmetrical
LFP
associated
severe
baseline,
keeping
hypothesis
dysfunction
contributes
MDD
pathophysiology.
These
preliminary
findings
indicate
may
offer
valuable
suffer
Larger
well-controlled
studies
are
warranted
examine
efficacy
treatment-refractory
mood
disorders
rigorous
fashion.
Major
depressive
disorder
(MDD)
is
a
highly
prevalent
and
disabling
disorder.
Despite
the
many
hypotheses
proposed
to
understand
molecular
pathophysiology
of
depression,
it
still
unclear.
Current
treatments
for
depression
are
inadequate
individuals,
because
limited
effectiveness,
delayed
efficacy
(usually
two
weeks),
side
effects.
Consequently,
novel
drugs
with
increased
speed
action
effectiveness
required.
Ketamine
has
shown
have
rapid,
reliable,
long-lasting
antidepressant
effects
in
treatment-resistant
MDD
patients
represent
breakthrough
therapy
MDD;
however,
concerns
regarding
its
efficacy,
potential
misuse,
remain.
In
this
review,
we
aimed
summarize
mechanisms
pharmacological
depression.
We
focused
on
fast
treatment
clarified
safety,
tolerability,
ketamine
metabolites
treatment,
along
review
mechanisms,
research
challenges,
future
clinical
prospects.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Фев. 9, 2023
Abstract
Alterations
in
energy
metabolism
are
associated
with
depression.
However,
the
role
of
glycolysis
pathogenesis
depression
and
underlying
molecular
mechanisms
remain
unexplored.
Through
an
unbiased
proteomic
screen
coupled
biochemical
verifications,
we
show
that
levels
lactate
dehydrogenase
A
(LDHA),
a
glycolytic
enzyme
catalyzes
L-lactate
production,
reduced
dorsomedial
prefrontal
cortex
(dmPFC)
stress-susceptible
mice
chronic
social
defeat
stress
(CSDS)
model.
Conditional
knockout
LDHA
from
brain
promotes
depressive-like
behaviors
both
male
female
mice,
accompanied
decreased
neuronal
excitability
dmPFC.
Moreover,
these
phenotypes
could
be
duplicated
by
knockdown
dmPFC
or
specifically
astrocytes.
In
contrast,
overexpression
reverses
phenotypic
changes
CSDS-susceptible
mice.
Mechanistic
studies
demonstrate
through
monocarboxylic
acid
transporter
2
(MCT2)
inhibiting
large-conductance
Ca
2+
-activated
potassium
(BK)
channel.
Together,
results
reveal
maintaining
to
prevent
behaviors.
Cell Research,
Год журнала:
2024,
Номер
34(3), С. 214 - 231
Опубликована: Фев. 8, 2024
Abstract
Flickering
light
stimulation
has
emerged
as
a
promising
non-invasive
neuromodulation
strategy
to
alleviate
neuropsychiatric
disorders.
However,
the
lack
of
neurochemical
underpinning
hampered
its
therapeutic
development.
Here,
we
demonstrate
that
flickering
triggered
an
immediate
and
sustained
increase
(up
3
h
after
flickering)
in
extracellular
adenosine
levels
primary
visual
cortex
(V1)
other
brain
regions,
function
frequency
intensity,
with
maximal
effects
observed
at
40
Hz
4000
lux.
We
uncovered
cortical
(glutamatergic
GABAergic)
neurons,
rather
than
astrocytes,
cellular
source,
intracellular
generation
from
AMPK-associated
energy
metabolism
pathways
(but
not
SAM-transmethylation
or
salvage
purine
pathways),
efflux
mediated
by
equilibrative
nucleoside
transporter-2
(ENT2)
molecular
pathway
responsible
for
generation.
Importantly,
20
80
Hz)
30
min
enhanced
non-rapid
eye
movement
(non-REM)
REM
sleep
2–3
mice.
This
somnogenic
effect
was
abolished
ablation
V1
superior
colliculus)
neurons
genetic
deletion
gene
encoding
ENT2
ENT1),
but
recaptured
chemogenetic
inhibition
focal
infusion
into
dose-dependent
manner.
Lastly,
also
promoted
children
insomnia
decreasing
onset
latency,
increasing
total
time,
reducing
waking
onset.
Collectively,
our
findings
establish
ENT2-mediated
signaling
basis
flickering-induced
unravel
novel
treatment
insomnia,
condition
affects
20%
world
population.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 2, 2025
Alzheimer's
disease
is
characterized
by
progressive
amyloid
deposition
and
cognitive
decline,
yet
the
pathological
mechanisms
treatments
remain
elusive.
Here
we
report
therapeutic
potential
of
low-intensity
40
hertz
blue
light
exposure
in
a
5xFAD
mouse
model
disease.
Our
findings
reveal
that
treatment
prevents
memory
decline
4-month-old
mice
motivation
loss
14-month-old
mice,
accompanied
restoration
glial
water
channel
aquaporin-4
polarity,
improved
brain
drainage
efficiency,
reduction
hippocampal
lipid
accumulation.
We
further
demonstrate
beneficial
effects
are
mediated
through
activation
vLGN/IGL-Re
visual
circuit.
Notably,
concomitant
use
anti-Aβ
antibody
with
demonstrates
soluble
Aβ
clearance
performance
mice.
These
offer
functional
evidence
on
Aβ-related
pathologies
suggest
its
as
supplementary
strategy
to
augment
efficacy
antibody-based
therapy.
Treatments
for
(AD)
limited.
Here,
authors
show
activates
circuit
boost
glymphatic
drainage,
enhances
memory,
motivation,
therapy
AD.
Chronobiology International,
Год журнала:
2025,
Номер
unknown, С. 1 - 23
Опубликована: Янв. 22, 2025
The
intricate
relationship
between
circadian
rhythms
and
mood
is
well-established.
Disturbances
in
sleep
often
precede
the
development
of
disorders,
such
as
major
depressive
disorder
(MDD),
bipolar
(BD),
seasonal
affective
(SAD).
Two
primary
factors,
intrinsic
clocks
light,
drive
natural
fluctuations
throughout
day,
mirroring
patterns
sleepiness
wakefulness.
Nearly
all
organisms
possess
that
coordinate
daily
rhythms,
with
light
serving
environmental
cue
to
synchronize
these
internal
timekeepers
24-hour
cycle.
Additionally,
directly
influences
states.
Disruptions
those
caused
by
jet
lag,
shift
work,
or
reduced
daylight
hours,
can
trigger
exacerbate
symptoms.
complex
subtle
connections
disruptions
dysregulation
suggest
focusing
solely
on
individual
clock
genes
insufficient
fully
understand
their
etiology
progression.
Instead,
instability
may
arise
from
systemic
misalignments
external
cycles
synchronization
clocks.
Here,
we
synthesize
past
research
independent
contributions
regulation,
drawing
particularly
insights
animal
studies
illuminate
fundamental
mechanisms
relevant
human
health.
