bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 17, 2024
Abstract
Psilocybin
is
a
psychedelic
tryptamine
that
has
emerged
as
potential
candidate
for
the
treatment
of
variety
conditions,
including
resistant
depression
and
post-traumatic
stress
disorder.
Clinical
trials
which
have
assessed
efficacy
psilocybin
these
conditions
report
rapid
sustained
improvement
in
patient-
clinician-rated
scores.
The
established
mechanism
action
psychedelics
such
agonism
serotonin
2A
receptor
(5HT
R),
however,
downstream
events
mediate
their
therapeutic
effects
remain
uncertain.
As
high
doses
are
known
to
induce
strong
perceptual
alterations,
an
additional
outstanding
question
whether
subperceptual
similar
molecular
psychoactive
dosages.
Here,
we
first
analysis
dose-
sex-dependent
transcriptional
changes
forebrains
female
male
mice
at
3
timepoints
(8
hours,
24
7
days)
following
single
administration
low
(0.25
mg/kg)
or
(1
doses.
Grouped
both
sexes
reveals
time-dependent
transcriptomic
alterations.
We
more
attenuation
females
low-dose
relative
males
treated
identically.
Females
also
responded
robustly
high-dose
8
with
signal
by
days.
A
notable
observation
was
persistent
effect
days,
outlasted
changes,
suggests
may
prolonged
biological
effects.
myriad
pathways
were
altered
depending
on
sex
timepoint,
but
common
features
included
functions
related
neuronal
differentiation,
neurogenesis,
signaling.
These
data
reveal
support
previous
studies
demonstrating
its
dendritogenesis.
Given
ongoing
clinical
interest
treating
mental
health
disorders,
our
results
suggest
sexually
divergent
should
be
considered
when
weighing
strategies.
Additional
consideration
given
temporal
vs
dosages
gene
transcription,
especially
timing
adjuvant
cognitive
behavioral
therapy.
The
circadian
clock
is
an
internal
timekeeper
system
that
regulates
biological
processes
through
a
central
and
peripheral
clocks
controlling
various
genes.
Basic
helix-loop-helix
ARNT-like
1
(BMAL1),
also
known
as
aryl
hydrocarbon
receptor
nuclear
translocator-like
protein
(ARNTL1),
key
component
of
the
clock.
deletion
BMAL1
alone
can
abolish
rhythms
human
body.
plays
critical
role
in
immune
cell
function.
Dysregulation
linked
to
immune-related
diseases
such
autoimmune
diseases,
infectious
cancer,
vice
versa.
This
review
highlights
significant
governing
cells,
including
their
development,
differentiation,
migration,
homing,
metabolism,
effector
functions.
study
explores
how
dysregulation
have
far-reaching
implications
potentially
contribute
onset
sepsis,
trauma.
Furthermore,
this
discusses
treatments
for
target
disorders.
Understanding
impact
on
function
provide
insights
into
pathogenesis
help
development
more
effective
treatment
strategies.
Targeting
has
been
demonstrated
achieve
good
efficacy
indicating
its
promising
potential
targetable
therapeutic
these
diseases.
Glia
are
increasingly
appreciated
as
serving
an
important
function
in
the
control
of
sleep
and
circadian
rhythms.
Glial
cells
Drosophila
mammals
regulate
daily
rhythms
locomotor
activity
well
homeostatic
rebound
following
deprivation.
In
addition,
they
contribute
to
proposed
functions
sleep,
with
different
mapping
varied
glial
subtypes.
Here,
we
discuss
recent
findings
rodent
models
establishing
a
role
glia
or
regulation
synaptic
plasticity,
brain
metabolism,
removal
cellular
debris
immune
challenges.
These
underscore
relevance
for
benefits
attributed
have
implications
understanding
neurobiological
mechanisms
underlying
associated
disorders.
CNS Neuroscience & Therapeutics,
Год журнала:
2024,
Номер
30(7)
Опубликована: Июль 1, 2024
Abstract
Background
Sleep
deprivation
(SD)
is
a
growing
global
health
problem
with
many
deleterious
effects,
such
as
cognitive
impairment.
Microglia
activation‐induced
neuroinflammation
may
be
an
essential
factor
in
this.
Propofol
has
been
shown
to
clear
sleep
debt
after
SD
rats.
This
study
aims
evaluate
the
effects
of
propofol‐induced
on
ameliorating
quality
impairment
and
decline
48
h
SD.
Methods
Almost
8–12‐week‐old
rats
were
placed
system
for
natural
or
continuous
Afterwards,
received
propofol
(20
mg·kg
−1
·h
,
6
h)
via
tail
slept
naturally.
The
Morris
water
maze
(MWM)
Y‐maze
test
assessed
spatial
learning
memory
abilities.
Rat
EEG/EMG
monitored
sleep.
expression
brain
muscle
Arnt‐like
protein
1
(BMAL1),
brain‐derived
neurotrophic
(BDNF)
hippocampus
BMAL1
hypothalamus
by
western
blot.
Enzyme‐linked
immunosorbent
assay
detected
IL‐6,
IL‐1β,
arginase
(Arg1),
IL‐10
levels
hippocampus.
Immunofluorescence
was
used
determine
microglia
well
morphological
changes.
Results
Compared
control
group,
sleep‐deprived
showed
poor
performance
both
MWM
test,
accompanied
disturbances
structure,
including
increased
total
time,
time
spent
delta
power
non‐rapid
eye
movement
In
addition,
induces
abnormal
circadian
rhythm
BMAL1,
activates
microglia,
causes
nerve
damage.
reversed
these
changes
saved
Furthermore,
treatment
significantly
reduced
hippocampal
IL‐1β
IL‐6
levels,
BDNF,
Arg1,
switched
surface
markers
from
inflammatory
M1
type
anti‐inflammatory
M2
type.
Conclusion
reduces
SD‐induced
disruption,
possibly
lowering
neuronal
inflammation
switching
phenotype
activated
state,
thus
exerting
neuroprotective
effects.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 13, 2025
Abstract
Microglia
are
specialized
resident
immune
cells
of
the
central
nervous
system
parenchyma
that
mediate
reactions
such
as
inflammatory
response
to
spinal
cord
injury
(SCI)
and
play
significant
roles
in
exacerbating
or
alleviating
disease
progression.
Previous
studies
have
suggested
ferroptosis,
a
newly
discovered
form
regulated
necrotic
cell
death,
plays
crucial
role
neuronal
dysfunction
loss
following
SCI;
however,
microglial
ferroptosis
SCI
underlying
mechanisms
remain
elusive.
Here,
we
elucidate
lipid
droplets
accumulate
microglia
facilitate
after
SCI.
Notably,
peaks
at
3
days
post-injury,
which
it
decreases.
Microglial
Period
2
(Per2)
expression
is
elevated
vivo,
this
change
highly
synchronized
with
changes
ferroptosis.
Using
conditional
knockout
mice,
observed
microglia-specific
Per2
promoted
neurological
function
recovery
by
suppressing
In
vitro,
overexpression
deficiency
amplified
mitigated
respectively.
RNA-seq
analysis,
found
Gpx4
was
downregulated
Per2.
Coimmunoprecipitation
(Co-IP)
demonstrated
directly
interacted
PPARα
further
regulate
Gpx4.
Furthermore,
degree
decreased
number
increased
treatment
inhibitor,
indicated
reducing
during
acute
phase
may
be
beneficial
for
dysfunction.
Overall,
our
results
indicate
determines
susceptibility
via
PPARα-Gpx4
axis,
suggest
has
potential
therapeutic
strategy
alleviate
motor
inhibiting
Circulation Research,
Год журнала:
2024,
Номер
134(6), С. 748 - 769
Опубликована: Март 14, 2024
Mammalian
physiology
and
cellular
function
are
subject
to
significant
oscillations
over
the
course
of
every
24-hour
day.
It
is
likely
that
these
daily
rhythms
will
affect
as
well
mechanisms
disease
in
central
nervous
system.
In
this
review,
we
attempt
survey
synthesize
emerging
studies
investigate
how
circadian
biology
may
influence
neurovascular
unit.
We
examine
clocks
operate
neural,
glial,
vascular
compartments,
review
regulate
cell-cell
signaling,
assess
interactions
with
aging
comorbidities,
finally
ask
whether
effects
disruptions
risk
progression
pathophysiology
cerebrovascular
disease.
Overcoming
identified
challenges
leveraging
opportunities
for
future
research
might
support
development
novel
circadian-based
treatments
stroke.
