Hyperexcitation of the glutamatergic neurons in lateral hypothalamus induced by chronic pain contributes to depression-like behavior and learning and memory impairment in male mice
Lianghui Meng,
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Xuefeng Zheng,
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Keman Xie
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et al.
Neurobiology of Stress,
Journal Year:
2024,
Volume and Issue:
31, P. 100654 - 100654
Published: June 1, 2024
Chronic
pain
can
induce
mood
disorders
and
cognitive
dysfunction,
such
as
anxiety,
depression,
learning
memory
impairment
in
humans.
However,
the
specific
neural
network
involved
anxiety-
depression-like
behaviors
caused
by
chronic
remains
poorly
understood.
In
this
study,
behavioral
test
results
showed
that
induced
behaviors,
male
mice.
c-Fos
immunofluorescence
fiber
photometry
recording
glutamatergic
neurons
LH
of
mice
with
were
selectively
activated.
Next,
normal
activated
using
optogenetic
chemogenetic
methods,
which
recapitulates
some
depressive-like
well
impairment,
but
not
anxiety-like
behavior.
Finally,
inhibition
pain,
effectively
relieved
impairment.
Taken
together,
our
findings
suggest
hyperexcitation
is
behavior
pain.
Language: Английский
Evans Blue Acts as a Selective Inhibitor of CaMKII‐α to Impede the Progression of TCL Identified by HTS
Jianru Tian,
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Aiqin Zhang,
No information about this author
Lansong Li
No information about this author
et al.
Cancer Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 4, 2025
T-cell
lymphoma
(TCL)
poses
a
significant
challenge
in
clinical
oncology,
characterized
by
its
aggressive
behavior
and
resistance
to
conventional
therapies.
Despite
considerable
research
efforts,
the
prognosis
for
TCL
patients
remains
poor,
primarily
due
lack
of
effective
therapeutic
strategies
that
can
inhibit
tumor
progression
metastasis.
In
this
study,
we
identified
CaMKII-α
as
potential
target
TCL.
To
explore
role
pathogenesis,
investigated
effects
on
cell
lines.
Protein
expression
levels
within
PI3K-AKT
signaling
pathway
were
assessed
using
western
blot
analysis.
Through
siRNA-mediated
gene
silencing,
downregulated
monitored
proliferation.
Furthermore,
Evans
Blue
(IC50
=
197.1
nM)
selective
small-molecule
inhibitor
through
high-throughput
screening
(HTS).
demonstrated
tumor-suppressive
effects,
potentially
inhibiting
proliferation
via
regulation
pathway.
Notably,
antitumor
effect
was
comparable
observed
with
genetic
ablation,
highlighting
novel
strategy
treatment
Language: Английский
GHS-R1a signaling drives anxiety-related behavior by shaping excitability of ventromedial hypothalamic neurons
Meng Zhang,
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Liu Yang,
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Xue Mi
No information about this author
et al.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: April 24, 2025
The
neural
substrates
of
anxiety
are
poorly
understood,
which
hinders
treatment
disorders.
Here
we
found,
αCaMKII+
neurons
in
the
ventral
medial
hypothalamic
nucleus
(VMH)
responded
to
stressors
with
increased
activity
male
mice,
both
under
physiological
conditions
and
after
repeated
restraint
stress.
Activation
VMH
were
necessary
sufficient
ameliorate
stress-induced
anxiety.
peripheral
metabolic
hormone
ghrelin
receptor
GHS-R1a
play
a
complex
role
emotion
regulation;
however,
mechanism
is
uncertain.
A
delayed
increase
expression
coincided
development
enhancement
anxiety-related
behavior.
promoted
behavior,
whereas
knockdown
had
opposite
effect.
upregulation
inhibited
excitability
neurons.
We
conclude
that
GHSR1a
signaling
drives
by
shaping
may
be
therapeutic
target
for
treating
disorders
such
as
post-traumatic
stress
disorder.
Language: Английский
The altered hypothalamic network functional connectivity in chronic insomnia disorder and regulation effect of acupuncture: a randomized controlled neuroimaging study
Wei Peng,
No information about this author
Hao Xu,
No information about this author
Chuanzhi Zhang
No information about this author
et al.
BMC Complementary Medicine and Therapies,
Journal Year:
2024,
Volume and Issue:
24(1)
Published: Nov. 14, 2024
The
hypothalamus
has
been
recognized
as
a
core
structure
in
the
sleep-wake
cycle.
However,
whether
neuroplasticity
of
is
involved
acupuncture
treatment
insomnia
remains
elusive.
We
recruited
42
patients
with
chronic
disorder
(CID)
and
23
matched
healthy
controls
(HCs),
CID
randomly
assigned
to
receive
real
(RA)
or
sham
(SA)
for
four
weeks.
Insomnia
severity
was
evaluated
using
Pittsburgh
Sleep
Quality
Index
(PSQI)
score,
resting-state
functional
connectivity
(rsFC)
assessed
via
magnetic
resonance
imaging
(fMRI).
In
cross-sectional
investigation,
showed
increased
rsFC
between
medial
(MH)
left
lateral
orbital
frontal
cortex
(LOFC),
bilateral
(MOFC)
compared
HCs.
longitudinal
experiment,
PSQI
scores
significantly
decreased
RA
group
(p
=
0.03)
but
not
SA
group.
Interestingly,
MH-LOFC
found
be
reduced
following
treatment.
addition,
altered
correlated
clinical
improvement
(r
-0.692,
p
0.006).
This
randomized
neuroimaging
study
provides
preliminary
evidence
that
may
improve
symptoms
by
restoring
circuits
associated
hypothalamic
subregions.
trial
registered
on
Chinese
Clinical
Trial
Registry
(
www.chictr.org.cn
)
identifier
(ChiCTR1800017092).
Registered
date:
11/07/2018.
Language: Английский
Ventromedial hypothalamus relays chronic stress inputs and exerts bidirectional regulation on anxiety state and related sympathetic activity
Frontiers in Cellular Neuroscience,
Journal Year:
2023,
Volume and Issue:
17
Published: Dec. 14, 2023
Chronic
stress
can
induce
negative
emotion
states,
including
anxiety
and
depression,
leading
to
sympathetic
overactivation
disturbed
physiological
homeostasis
in
peripheral
tissues.
While
anxiety-related
neural
circuitry
integrates
chronic
information
modulates
nervous
system
(SNS)
activity,
the
critical
nodes
linking
activity
still
need
be
clarified.
In
our
previous
study,
we
demonstrated
that
ventromedial
hypothalamus
(VMH)
is
involved
integrating
inputs
exerting
influence
on
activity.
However,
underlying
synaptic
electrophysiological
mechanisms
remain
elusive.
this
combined
vitro
recordings,
behavioral
tests,
optogenetic
manipulations,
SNS
analyses
explore
role
of
VMH
Results
showed
played
an
important
bidirectionally
regulating
anxiety-like
behavior
excitation.
enhanced
excitatory
into
neurons
by
strengthening
connection
with
paraventricular
(PVN),
hence
promoting
tone
outflow,
factor
contributing
development
metabolic
imbalance
tissues
cardiovascular
diseases.
Language: Английский
Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder
Ai-Xi Su,
No information about this author
Zi-Jie Ma,
No information about this author
Zong-Yin Li
No information about this author
et al.
Frontiers in Psychiatry,
Journal Year:
2024,
Volume and Issue:
15
Published: May 13, 2024
To
examine
serum
concentrations
of
neurotensin,
pannexin-1
and
sestrin-2,
their
correlations
with
subjective
objective
sleep
quality
cognitive
function
in
the
patients
chronic
insomnia
disorder
(CID).
Sixty-five
CID
were
enrolled
continuously
fifty-six
good
sleepers
same
period
served
as
healthy
controls
(HCs).
Serum
levels
sestrin-2
measured
by
enzyme-linked
immunosorbent
assays.
Sleep
was
assessed
Pittsburgh
Quality
Index
(PSQI)
polysomnography,
mood
evaluated
17-item
Hamilton
Depression
Rating
Scale.
General
Chinese-Beijing
Version
Montreal
Cognitive
Assessment
spatial
memory
Blue
Velvet
Arena
Test
(BVAT).
Relative
to
HCs,
sufferers
had
higher
neurotensin
(t=5.210,
p<0.001)
(Z=-4.169,
p<0.001),
lower
level
(Z=-2.438,
p=0.015).
In
terms
measures,
positively
associated
total
time
(r=0.562,
p=0.002)
efficiency
(r=0.588,
p=0.001),
negatively
wake
after
onset
(r=-0.590,
p=0.001)
p=0.001);
percentage
rapid
eye
movement
(r=0.442,
p=0.016)
non-rapid
stage
2
(r=-0.394,
p=0.034).
Adjusted
for
sex,
age
HAMD,
still
above
but
only
(r=-0.446,
p=0.022).
However,
these
biomarkers
showed
no
significant
(PSQI
score).
mean
erroneous
distance
BVAT.
depression,
MoCA
score
(r=-0.257,
p=0.044),
BVAT
(r=0.270,
p=0.033).
The
increased
decreased
levels,
indicating
neuron
dysfunction,
which
could
be
related
poor
dysfunction
objectively.
Language: Английский