bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 17, 2023
Alzheimer's
disease
(AD)
patients
exhibit
neuropsychiatric
symptoms
that
extend
beyond
classical
cognitive
deficits,
suggesting
involvement
of
subcortical
areas.
Here,
we
investigated
the
role
midbrain
dopamine
(DA)
neurons
in
AD
using
amyloid
+
tau-driven
3xTg-AD
mouse
model.
We
found
deficits
reward-based
operant
learning
mice,
possible
VTA
DA
neuron
dysregulation.
Physiological
assessment
revealed
hyperexcitability
and
disrupted
firing
caused
by
reduced
activity
small-conductance
calcium-activated
potassium
(SK)
channels.
RNA
sequencing
from
contents
single
patch-clamped
(Patch-seq)
identified
up-regulation
SK
channel
modulator
casein
kinase
2
(CK2).
Pharmacological
inhibition
CK2
restored
normal
patterns
mice.
These
findings
shed
light
on
a
complex
interplay
between
circuits
AD,
paving
way
for
novel
treatment
strategies.
Biomedicines,
Год журнала:
2024,
Номер
12(3), С. 643 - 643
Опубликована: Март 13, 2024
Traumatic
injury
to
the
brain
and
spinal
cord
(neurotrauma)
is
a
common
event
across
populations
often
causes
profound
irreversible
disability.
Pathophysiological
responses
trauma
exacerbate
damage
of
an
index
injury,
propagating
loss
function
that
central
nervous
system
(CNS)
cannot
repair
after
initial
resolved.
The
way
in
which
lost
consequence
complex
array
mechanisms
continue
chronic
phase
post-injury
prevent
effective
neural
repair.
This
review
summarises
events
traumatic
(TBI)
(SCI),
comprising
description
current
clinical
management
strategies,
summary
known
cellular
molecular
secondary
their
role
prevention
A
discussion
emerging
approaches
promote
neuroregeneration
CNS
presented.
barriers
promoting
neurotrauma
are
pathways
cell
types
occur
on
level.
presents
challenge
traditional
pharmacological
targeting
single
pathways.
It
suggested
novel
multiple
or
using
combinatorial
therapies
may
yield
sought-after
recovery
for
future
patients.
Journal of Orthopaedic Surgery and Research,
Год журнала:
2024,
Номер
19(1)
Опубликована: Июль 2, 2024
Abstract
Spinal
cord
injury
(SCI)
is
a
severe
condition
with
an
extremely
high
disability
rate.
It
mainly
manifested
as
the
loss
of
motor,
sensory
and
autonomic
nerve
functions
below
site.
High-frequency
transcranial
magnetic
stimulation,
recently
developed
neuromodulation
method,
can
increase
motor
function
in
mice
spinal
injury.
This
study
aimed
to
explore
possible
mechanism
by
which
stimulation
(TMS)
restores
after
SCI.
A
complete
T8
transection
model
was
established
mice,
were
treated
daily
15
Hz
high-frequency
stimulation.
The
BMS
used
evaluate
Western
blotting
immunofluorescence
detect
expression
Connexin43
(CX43)
autophagy-related
proteins
vivo
vitro,
correlation
analysis
performed
relationships
among
autophagy,
CX43
recovery
SCI
mice.
observe
effect
on
mTOR
pathway
members.
In
control
group,
significantly
decreased,
microtubule-associated
protein
1
A/1b
light
chain
3
(LC3II)
P62
increased
4
weeks
transection.
After
level
levels
LC3II
primary
astrocytes.
group
greater
than
that
group.
inhibit
CX43,
negatively
regulates
autophagic
flux.
HF-rTMS
mTOR,
p-mTOR
p-S6.
Our
experiments
showed
rTMS
restore
hindlimb
via
regulation
Cx43-autophagy
loop
activation
signalling
pathway.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 8, 2024
Abstract
Alzheimer’s
disease
(AD)
patients
exhibit
neuropsychiatric
symptoms
that
extend
beyond
classical
cognitive
deficits,
suggesting
involvement
of
subcortical
areas.
Here,
we
investigated
the
role
midbrain
dopamine
(DA)
neurons
in
AD
using
amyloid
+
tau-driven
3xTg-AD
mouse
model.
We
found
deficits
reward-based
operant
learning
mice,
possible
VTA
DA
neuron
dysregulation.
Physiological
assessment
revealed
hyperexcitability
and
disrupted
firing
caused
by
reduced
activity
small-conductance
calcium-activated
potassium
(SK)
channels.
RNA
sequencing
from
contents
single
patch-clamped
(Patch-seq)
identified
up-regulation
SK
channel
modulator
casein
kinase
2
(CK2),
which
corroborated
immunohistochemical
protein
analysis.
Pharmacological
inhibition
CK2
restored
normal
patterns
mice.
These
findings
identify
a
mechanism
ion
dysregulation
could
contribute
to
behavioral
abnormalities
AD,
paving
way
for
novel
treatment
strategies.
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(39)
Опубликована: Сен. 18, 2024
Adult
central
nervous
system
(CNS)
neurons
down-regulate
growth
programs
after
injury,
leading
to
persistent
regeneration
failure.
Coordinated
lipids
metabolism
is
required
synthesize
membrane
components
during
axon
regeneration.
However,
also
function
as
cell
signaling
molecules.
Whether
lipid
contributes
remains
unclear.
In
this
study,
we
showed
that
lipin1
orchestrates
mechanistic
target
of
rapamycin
(mTOR)
and
STAT3
pathways
determine
We
established
an
mTOR-lipin1-phosphatidic
acid/lysophosphatidic
acid-mTOR
loop
acts
a
positive
feedback
inhibitory
signaling,
contributing
the
suppression
CNS
following
injury.
addition,
knockdown
(KD)
enhances
corticospinal
tract
(CST)
sprouting
unilateral
pyramidotomy
promotes
CST
complete
spinal
cord
injury
(SCI).
Furthermore,
KD
sensory
SCI.
Overall,
our
research
reveals
functions
regulator
coordinate
mTOR
in
highlights
potential
promising
therapeutic
for
promoting
motor
axons
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 28, 2024
Abstract
Traumatic
brain
injury
(TBI)
is
a
risk
factor
for
neurodegeneration,
however
little
known
about
how
different
neuron
types
respond
to
this
kind
of
injury.
In
study,
we
follow
neuronal
populations
over
several
months
after
single
mild
TBI
(mTBI)
assess
long
ranging
consequences
at
the
level
single,
transcriptionally
defined
classes.
We
find
that
stress
responsive
Activating
Transcription
Factor
3
(ATF3)
defines
population
cortical
neurons
mTBI.
show
activate
ATF3
upregulate
stress-related
genes
while
repressing
many
genes,
including
commonly
used
markers
these
cell
types.
Using
an
inducible
reporter
linked
ATF3,
genetically
mark
damaged
cells
track
them
time.
Notably,
in
layer
V
undergoes
death
acutely
injury,
another
II/III
survives
term
and
retains
ability
fire
action
potentials.
To
investigate
mechanism
controlling
death,
silenced
candidate
response
pathways.
found
axon
kinase
MAP3K12,
also
as
dual
leucine
zipper
(DLK),
required
death.
This
work
provides
rationale
targeting
DLK
signaling
pathway
therapeutic
intervention
traumatic
Beyond
this,
our
novel
approach
mild,
subclinical
can
inform
understanding
susceptibility
repeated
impacts.
