Intermittent Fasting Ameliorates β‐Amyloid Deposition and Cognitive Impairment Accompanied by Decreased Lipid Droplet Aggregation Within Microglia in an Alzheimer's Disease Model
Molecular Nutrition & Food Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 22, 2025
ABSTRACT
Scope:
Alzheimer's
disease
(AD)
is
the
most
prevalent
form
of
dementia,
lack
effective
therapeutic
interventions.
In
this
study,
we
investigate
impact
intermittent
fasting
(IF),
an
alternative
strategy
calorie
restriction,
on
cognitive
functions
and
AD‐like
pathology
in
a
transgenic
mouse
model
AD.
Methods
results:
APP/PS1
mice
at
6
months
were
randomly
allocated
to
two
dietary
groups:
one
receiving
ad
libitum
(AL)
feeding
other
undergoing
IF
for
1
month.
Y
maze,
Barnes
western
blotting,
immunofluorescence
employed.
Behavioral
assessments
revealed
that
APP/PS1‐IF
group
demonstrated
notable
improvements
function
compared
AL
group.
Further
analysis
showed
microglia
exhibited
enhanced
phagocytic
activity,
characterized
by
prominent
enlargement
soma
reduced
complexity
their
processes.
Importantly,
significantly
decreased
accumulation
lipid
droplets
(LDs)
within
microglia.
These
with
less
LDs
may
contribute
β‐amyloid
(Aβ)
phagocytosis,
thereby
ameliorating
Aβ
deposition
brains
mice.
Conclusion:
Our
findings
demonstrate
ameliorates
amyloid
deficits
AD
mice,
which
associated
reduction
microglia,
providing
support
use
intervention
against
pathology.
Язык: Английский
Therapeutic effects of orexin-A in sepsis-associated encephalopathy in mice
Journal of Neuroinflammation,
Год журнала:
2024,
Номер
21(1)
Опубликована: Май 17, 2024
Sepsis-associated
encephalopathy
(SAE)
causes
acute
and
long-term
cognitive
deficits.
However,
information
on
the
prevention
treatment
of
dysfunction
after
sepsis
is
limited.
The
neuropeptide
orexin-A
(OXA)
has
been
shown
to
play
a
protective
role
against
neurological
diseases
by
modulating
inflammatory
response
through
activation
OXR1
OXR2
receptors.
OXA
in
mediating
neuroprotective
effects
SAE
not
yet
reported.
Язык: Английский
Hypocretin‐1/Hypocretin Receptor 1 Regulates Neuroplasticity and Cognitive Function through Hippocampal Lactate Homeostasis in Depressed Model
Advanced Science,
Год журнала:
2024,
Номер
11(38)
Опубликована: Авг. 9, 2024
Abstract
Cognitive
dysfunction
is
not
only
a
common
symptom
of
major
depressive
disorder,
but
also
more
residual
after
antidepressant
treatment
and
risk
factor
for
chronic
recurrent
disease.
The
disruption
hypocretin
regulation
known
to
be
associated
with
depression,
however,
their
exact
correlation
remains
elucidated.
Hypocretin‐1
levels
are
increased
in
the
plasma
hypothalamus
from
unpredictable
mild
stress
(CUMS)
model
mice.
Excessive
hypocretin‐1
conducted
receptor
1
(HCRTR1)
reduced
lactate
production
brain‐derived
neurotrophic
(BDNF)
expression
by
hypoxia‐inducible
factor‐1α
(HIF‐1α),
thus
impairing
adult
hippocampal
neuroplasticity,
cognitive
impairment
CUMS
model.
Subsequently,
it
found
that
HCRTR1
antagonists
can
reverse
these
changes.
direct
effect
on
behavior
further
confirmed
intraventricular
injection
microPET‐CT
rats.
In
addition,
mechanisms
validated
astrocytes
neurons
vitro.
Moreover,
phenotypes
changes
molecules
transport
pathway
duplicated
specifically
knockdown
astrocytes.
summary,
results
provide
molecular
functional
insights
involvement
hypocretin‐1‐HCRTR1
altered
function
depression.
Язык: Английский
The interaction between orexin, sleep deprivation and Alzheimer’s disease: Unveiling an Emerging Connection
The Journal of Physiological Sciences,
Год журнала:
2025,
Номер
75(1), С. 100004 - 100004
Опубликована: Март 1, 2025
Язык: Английский
Modelling orexinergic system in ageing in the African turquoise killifish
Biogerontology,
Год журнала:
2025,
Номер
26(2)
Опубликована: Март 14, 2025
Abstract
The
orexinergic
system
is
anatomically
and
functionally
conserved
in
almost
all
vertebrates,
the
role
healthy
ageing
age-associated
diseases
has
been
studied
mammals.
Here,
we
review
main
findings
on
age-related
regulation
of
mammals,
including
human
patients
highlights
how
fish
Nothobranchius
furzeri
serves
as
an
exceptional
model
to
spearhead
research
unravel
intricate
mechanisms
underlying
during
ageing.
brain
this
teleost
characterized
by
presence
neurodegenerative
processes
similar
those
associated
with
pathologies
rather
than
We
present
in-depth
summary
discussion
groundbreaking
advances
understanding
neuroanatomical
organization
system,
its
pivotal
mammalian
models,
profound
involvement
diseases.
Язык: Английский
Longitudinal Evaluation of the Detection Potential of Serum Oligoelements Cu, Se and Zn for the Diagnosis of Alzheimer’s Disease in the 3xTg-AD Animal Model
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(8), С. 3657 - 3657
Опубликована: Апрель 12, 2025
Alzheimer’s
disease
(AD)
is
a
progressive
neurodegenerative
disorder
characterized
by
the
accumulation
of
β-amyloid
(Aβ)
and
hyperphosphorylated
tau,
leading
to
neuroinflammation,
oxidative
stress,
neuronal
death.
Early
detection
AD
remains
challenge,
as
clinical
manifestations
only
emerge
in
advanced
stages,
limiting
therapeutic
interventions.
Minimally
invasive
biomarkers
are
essential
for
early
identification
monitoring
progression.
This
study
aims
evaluate
sensitivity
relationship
between
serum
oligoelement
levels
progression
3xTg-AD
model.
Transgenic
mice
C57BL/6
controls
were
evaluated
over
12
months
through
quantification
using
inductively
coupled
plasma
mass
spectrometry
(ICP-MS),
Aβ
deposition
via
immunohistochemistry,
cognitive
assessments
memory
tests
(Morris
water
maze
novel
object
recognition
test),
well
spontaneous
locomotion
analysis
open
field
test.
The
results
demonstrated
that
oligoelements
(copper,
zinc,
selenium)
sensitive
detecting
alterations
group,
preceding
motor
deficits.
Immunohistochemistry
was
performed
qualitative
purposes,
confirming
presence
CNS
transgenic
animals.
Up
third
month,
labeling
moderate
restricted
cell
bodies;
from
fifth
month
onward,
evident
extracellular
deposits
emerged.
Behavioral
assessment
indicated
impairments
spatial
episodic
memory,
altered
locomotor
patterns
mice.
These
findings
reinforce
variations
may
be
associated
with
processes,
including
stress
synaptic
dysfunction.
Thus,
emerges
promising
approach
diagnosis
progression,
potentially
contributing
development
new
strategies.
Язык: Английский
Selective Orexin 2 Receptor Blockade Alleviates Cognitive Impairments and the Pathological Progression of Alzheimer’s Disease in 3xTg-AD Mice
The Journals of Gerontology Series A,
Год журнала:
2024,
Номер
79(7)
Опубликована: Апрель 28, 2024
Abstract
The
orexin
system
is
closely
related
to
the
pathogenesis
of
Alzheimer’s
disease
(AD).
Orexin-A
aggravates
cognitive
dysfunction
and
increases
amyloid
β
(Aβ)
deposition
in
AD
model
mice,
but
studies
different
dual
receptor
(OXR)
antagonists
have
shown
inconsistent
results.
Our
previous
study
revealed
that
OX1R
blockade
deficits
pathological
progression
3xTg-AD
effects
OX2R
its
potential
mechanism
not
been
reported.
In
present
study,
was
blocked
by
oral
administration
selective
antagonist
MK-1064,
on
neuropsychiatric
symptoms
mice
were
evaluated
via
behavioral
tests.
Then,
immunohistochemistry,
western
blotting,
ELISA
used
detect
Aβ
deposition,
tau
phosphorylation,
neuroinflammation,
electrophysiological
wheel-running
activity
recording
recorded
observe
hippocampal
synaptic
plasticity
circadian
rhythm.
results
showed
ameliorated
dysfunction,
improved
LTP
depression,
increased
expression
PSD-95,
alleviated
anxiety-
depression-like
behaviors
rhythm
disturbances
reduced
pathology,
neuroinflammation
brains
mice.
These
indicated
chronic
exerts
neuroprotective
reducing
pathology
at
least
partly
through
improving
disturbance
sleep-wake
cycle
might
be
a
target
for
prevention
treatment
AD;
however,
which
needs
further
investigated.
Язык: Английский
WuYou Decoction effectively reduces neuronal damage, synaptic dysfunction, and Aβ production in rats exposed to chronic sleep deprivation by modulating the Aβ-related enzymes and SIRT1/Nrf2/NF-κB pathway
Journal of Ethnopharmacology,
Год журнала:
2024,
Номер
unknown, С. 118939 - 118939
Опубликована: Окт. 1, 2024
Язык: Английский