Exploring the parity paradox: Differential effects on neuroplasticity and inflammation by APOEe4 genotype at middle age
Brain Behavior and Immunity,
Год журнала:
2024,
Номер
120, С. 54 - 70
Опубликована: Май 19, 2024
Язык: Английский
Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats
Biology of Sex Differences,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 5, 2025
Abstract
Background
Alzheimer’s
disease
(AD)
disproportionately
and
uniquely
affects
females,
these
sex
differences
are
further
exacerbated
by
the
presence
of
Apolipoprotein
(APOE)
ε4
alleles,
top
genetic
risk
factor
for
late-onset
AD.
To
expand
our
understanding
about
how
AD
might
differentially
influence
males
this
study
explores
APOEε4
hippocampal
neurogenesis
microglia,
key
neuroplastic
markers
involved
in
pathogenesis,
differently
middle-aged
rats.
Methods
A
rat
model
expressing
humanized
(h)
allele
was
characterized
to
examine
adult
(neural
progenitor
cells
new-born
neurons)
immune
(microglia)
dentate
gyrus
hippocampus
13
month-old
male
female
Results
We
observed
basal
at
middle
age,
as
wildtype
rats
had
greater
densities
neural
neurons
than
Male
hAPOEε4
exhibited
fewer
cells,
neurons,
more
microglia
On
other
hand,
Interestingly,
females
regardless
genotype.
Correlations
were
conducted
elucidate
any
relationships
between
biomarkers.
Notably,
there
a
significant
positive
correlation
negative
but
only
Conclusion
In
contrast
clear
pattern
effects
on
males,
unaltered
levels
increased
density
neurons.
Furthermore,
significantly
correlated
within
not
females.
This
suggests
that
may
be
presenting
compensatory
response
genotype
age.
Collectively,
results
exemplify
importance
thoroughly
examining
influences
endophenotypes,
it
reveal
sex-specific
pathways
protective
mechanisms
relevant
Язык: Английский
Interactions between menopause and high‐fat diet on cognition and pathology in a mouse model of Alzheimer's disease
Alzheimer s & Dementia,
Год журнала:
2025,
Номер
21(3)
Опубликована: Март 1, 2025
Abstract
INTRODUCTION
Post‐menopausal
women
constitute
about
two‐thirds
of
those
with
Alzheimer's
disease
(AD).
Menopause
increases
dementia
risk
by
heightening
the
likelihood
metabolic
disease,
a
well‐known
factor
for
dementia.
We
aimed
to
determine
effects
menopause
and
high‐fat
diet
(HF)
on
cognitive
pathological
outcomes
in
an
AD
mouse
model.
METHODS
At
3
months
old,
App
NL‐F
mice
received
4‐vinylcyclohexene
diepoxide
(menopause
model)
or
vehicle
were
placed
control
(10%
fat)
HF
(60%
until
10
old.
RESULTS
An
interaction
between
led
impaired
recognition
memory.
No
observed
amyloid
pathology.
However,
induced
alterations
microglial
response,
white
matter,
hippocampal
neurogenesis.
DISCUSSION
This
work
highlights
need
model
endocrine
aging
animal
models
contributes
further
understanding
health
context
AD.
Highlights
The
combination
early
onset
impairment.
increased
pathology
hippocampus.
increase
microglia
density
decrease
myelin
corpus
callosum.
altered
neurogenesis
diet‐dependent
manner.
Язык: Английский
Chronic phase advances reduces recognition memory and increases vascular cognitive dementia-like impairments in aged mice
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Апрель 2, 2024
Abstract
Disrupted
or
atypical
light–dark
cycles
disrupts
synchronization
of
endogenous
circadian
clocks
to
the
external
environment;
extensive
rhythm
desynchrony
promotes
adverse
health
outcomes.
Previous
studies
suggest
that
disrupted
rhythms
promote
neuroinflammation
and
neuronal
damage
post-ischemia
in
otherwise
healthy
mice,
however,
few
date
have
evaluated
these
risks
with
aging.
Because
most
strokes
occur
aged
individuals,
we
sought
identify
whether,
addition
being
a
risk
factor
for
poor
ischemic
outcome,
disruption
can
increase
vascular
cognitive
impairment
dementia
(VCID).
We
hypothesized
repeated
6
h
phase
advances
(chronic
jet
lag;
CJL)
8
weeks
alters
cerebrovascular
architecture
leading
increased
impairments
mice.
Female
CJL
mice
displayed
impaired
spatial
processing
during
spontaneous
alternation
task
reduced
acquisition
auditory-cued
associative
learning.
Male
retention
learning
24
following
acquisition.
tortuosity
isocortex,
associated
disease.
These
results
demonstrate
sex-specific
coinciding
structural
changes
vasculature
brain.
highlight
may
accelerate
aged-related
functional
decline
could
be
crucial
target
against
disease
progression.
Язык: Английский
Long-term saturated fat-enriched diets impair hippocampal learning and memory processes in a sex-dependent manner
Neuropharmacology,
Год журнала:
2024,
Номер
259, С. 110108 - 110108
Опубликована: Авг. 10, 2024
Consumption
of
saturated
fat-enriched
diets
during
adolescence
has
been
closely
associated
with
the
reduction
hippocampal
synaptic
plasticity
and
impairment
cognitive
function.
Nevertheless,
effect
long-term
intake
these
foods
not
yet
studied.
In
present
study,
we
have
investigated
a
treatment,
lasting
for
40
weeks,
diet
enriched
in
fat
(SOLF)
on
i)
spatial
learning
memory,
ii)
transmission
plasticity,
iii)
gene
expression
levels
aged
male
female
mice.
Our
findings
reveal
that
SOLF
detrimental
impact
memory
mechanisms,
such
as
potentiation
(LTP),
downregulates
Gria1
specifically
males.
females,
Gria1/2/3
Grin1/2A/2B
glutamate
receptor
subunits
well
some
proinflammatory
interleukins.
These
highlight
importance
considering
sex-specific
factors
when
assessing
effects
high-fat
cognition
brain
plasticity.
Язык: Английский
Effects of Menopause and High Fat Diet on Metabolic Outcomes in a Mouse Model of Alzheimer’s Disease
Journal of Alzheimer s Disease,
Год журнала:
2024,
Номер
101(4), С. 1177 - 1194
Опубликована: Окт. 8, 2024
About
two-thirds
of
those
with
Alzheimer's
disease
(AD)
are
women,
most
whom
post-menopausal.
Menopause
accelerates
dementia
risk
by
increasing
the
for
metabolic,
cardiovascular,
and
cerebrovascular
diseases.
Mid-life
metabolic
(obesity,
diabetes/prediabetes)
is
a
well-known
factor
dementia.
A
high
fat
diet
can
lead
to
poor
health
in
both
humans
rodents.
Язык: Английский
Exploring the parity paradox: Differential effects on neuroplasticity and neuroinflammation by APOEe4 genotype at middle-age
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 13, 2023
Abstract
Female
sex
and
Apolipoprotein
E
(APOE)
ε4
genotype
are
top
non-modifiable
risk
factors
for
Alzheimer’s
disease
(AD).
Although
female-unique
experiences
like
parity
(pregnancy
motherhood)
have
positive
effects
on
neuroplasticity
at
middle
age,
previous
pregnancy
may
also
contribute
to
AD
risk.
To
explore
these
seemingly
paradoxical
long-term
of
parity,
we
investigated
the
impact
with
APOEε4
by
examining
behavioural
neural
biomarkers
brain
health
in
middle-aged
female
rats.
Our
findings
show
that
primiparous
(parous
one
time)
hAPOEε4
rats
display
increased
use
a
non-spatial
cognitive
strategy
exhibit
decreased
number
recruitment
new-born
neurons
ventral
dentate
gyrus
hippocampus
response
spatial
working
memory
retrieval.
Furthermore,
primiparity
synergistically
modulate
neuroinflammatory
markers
hippocampus.
Collectively,
demonstrate
confers
an
added
present
reduced
activity
engagement
as
well
elevated
pro-inflammatory
signaling,
underscores
importance
considering
female-specific
research.
Highlights
made
more
errors
used
Primiparous
Parity
neurogenesis
wildtype
rats,
but
it
had
less
active
new
retrieval
affect
neuroimmune
milieu
region-specific
manner
Язык: Английский
Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 12, 2024
Abstract
Objective:
White
matter
hyperintensities
(WMH)
on
brain
MRI
images
are
the
most
common
feature
of
cerebral
small
vessel
disease
(CSVD).
Studies
have
yielded
divergent
findings
modifiable
risk
factors
for
WMH
and
WMH’s
impact
cognitive
decline.
Mounting
evidence
suggests
sex
differences
in
burden
subsequent
effects
cognition.
Thus,
we
aimed
to
identify
sex-specific
WMH.
We
then
explored
whether
there
were
associations
longitudinal
clinical
dementia
outcomes.
Methods:
Participants
aged
49–89
years
recruited
at
memory
clinics
underwent
a
T2-weighted
fluid-attenuated
inversion
recovery
(FLAIR)
3T
scan
measure
volume.
two
additional
follow-up
visits,
1–2
apart,
where
rating
sum
boxes
(CDR-SB)
scores
measured.
first
which
known
significant
when
tested
sex-interaction
effect.
additionally
stratified
by
sex.
see
is
longitudinally
associated
with
that
sex-specific.
Results:
The
study
utilized
data
from
713
participants
(241
males,
472
females)
mean
age
72.3
72.8
males
females,
respectively.
57.3%
59.5%
diagnosed
mild
impairment
(MCI)
40.7%
39.4%
Of
participants,
181
had
CDR-SB
available
three
time
points.
Compared
females
showed
stronger
association
Type
2
Diabetes
was
greater
but
not
males.
Finally,
baseline
worse
outcomes
Discussion:
Elderly
an
accelerated
increase
cerebrovascular
as
they
age,
subsequently
more
vulnerable
decline
due
CSVD.
Additionally,
susceptible
consequences
diabetes.
These
emphasize
importance
considering
examining
Future
research
should
explore
underlying
mechanisms
driving
these
personalized
prevention
treatment
strategies.
Clinical
trial
registration:
BICWALZS
registered
Korean
National
Trial
Registry
(Clinical
Research
Information
Service;
identifier,
KCT0003391).
Registration
Date
2018/12/14.
Язык: Английский
The Effects of Diet-Induced Obesity on Cerebral Microvascular Bioenergetics
Опубликована: Янв. 1, 2024
Obesity
is
a
worldwide
epidemic
but
especially
concern
in
the
United
States
with
over
40%
of
population
being
obese.
known
to
cause
increased
metabolic
demand,
systemic
inflammation,
peripheral
vascular
dysfunction,
and
levels
oxidative
stress
reactive
oxygen
species
(ROS).
However,
role
obesity
on
cerebrovascular
bioenergetic
function
has
not
been
fully
elucidated.
This
study
aimed
determine
impact
diet-induced
bioenergetics.
72,
6-month-old
C57Bl/6
male
female
mice
were
randomized
into
control
HFD
groups.
Control
subjected
feeding
standard
chow
(18%
fat,
24%
protein,
58%
carbohydrate),
while
high-fat
diet
(60%
20%
carbohydrate)
for
4
months
(18
weeks).
Following
18
weeks,
euthanized,
brains
collected.
The
hypothalamus
was
removed
saved
addition
coronal
section.
remaining
brain
homogenized
cerebral
microvessels
(CMVs)
isolated
assess
bioenergetics
using
cell
Mito
test
Glyco
Seahorse
Bioflux
Analyzer.
Glucose
transporters
tissue
also
measured
Western
Blotting.
Our
data
showed
that
HFD-fed
significantly
(p
Язык: Английский
Sex-specific risk factors and clinical dementia outcomes for white matter hyperintensities in a large South Korean cohort
Alzheimer s Research & Therapy,
Год журнала:
2024,
Номер
16(1)
Опубликована: Ноя. 1, 2024
White
matter
hyperintensities
(WMH)
on
brain
MRI
images
are
the
most
common
feature
of
cerebral
small
vessel
disease
(CSVD).
Studies
have
yielded
divergent
findings
modifiable
risk
factors
for
WMH
and
WMH's
impact
cognitive
decline.
Mounting
evidence
suggests
sex
differences
in
burden
subsequent
effects
cognition.
Thus,
we
aimed
to
identify
sex-specific
WMH.
We
then
explored
whether
there
were
associations
longitudinal
clinical
dementia
outcomes.
Язык: Английский