Increased Cerebral Level of P2X7R in a Tauopathy Mouse Model by PET Using [18F]GSK1482160
ACS Chemical Neuroscience,
Год журнала:
2024,
Номер
15(11), С. 2112 - 2120
Опубликована: Май 22, 2024
Neuroinflammation
plays
an
important
role
in
Alzheimer's
disease
and
primary
tauopathies.
The
aim
of
the
current
study
was
to
map
[18F]GSK1482160
for
imaging
purinergic
P2X7R
tauopathy
mouse
models.
Small
animal
PET
performed
using
widely
used
models
(APP/PS1,
5×FAD,
3×Tg),
4-repeat
(rTg4510)
mice,
age-matched
wild-type
mice.
Increased
uptake
observed
brains
7-month-old
rTg4510
mice
compared
3-month-old
A
positive
correlation
between
hippocampal
tau
[18F]APN-1607
found
No
significant
differences
APP/PS1
5×FAD
or
3×Tg
Immunofluorescence
staining
further
indicated
distribution
P2X7Rs
with
accumulation
inclusion.
These
findings
provide
vivo
evidence
increased
level
Язык: Английский
Hippocampal purinergic P2X7 receptor level is increased in Alzheimer’s disease patients, and associated with amyloid and tau pathologies
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 28, 2024
Abstract
INTRODUCTION
The
purinergic
receptor
P2X7R,
which
is
expressed
on
microglia
and
astrocytes,
plays
an
important
role
in
Alzheimer’s
disease
(AD).
We
aimed
to
characterize
the
alterations
P2X7R
expression
AD
patients
by
APOE
ε4
allele,
age
sex,
as
well
its
association
with
amyloid
tau
pathology.
METHODS
staining
quantitative
analysis
of
amyloid,
tau,
astrocytes
were
performed
postmortem
hippocampal
tissues
from
35
patients;
31
nondemented
controls;
caudate/putamen
tissue
corticobasal
degeneration
(CBD),
progressive
supranuclear
palsy
(PSP)
bran
aged
3×Tg
mouse
model
AD.
RESULTS
Activated
reactive
observed
hippocampi
exhibited
altered
morphology
denser
cells
pronounced
ramifications.
Hippocampal
intensity
was
greater
subfields
than
those
controls
correlated
level
Braak
stage
not
affected
APOEε4
or
age.
increased
around
Aβ
plaques,
cerebral
angiopathy,
inclusions
hippocampus
CBD
PSP
patients.
DISCUSSION
found
compared
non-demented
control,
pathologies.
a
potential
marker
for
neuroinflammation
Язык: Английский
Increased regional P2X7R uptake detected by [18F]GSK1482160 PET in a tauopathy mouse model
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 28, 2024
Abstract
Neuroinflammation
plays
an
important
role
in
Alzheimer’s
disease
and
primary
tauopathies.
The
aim
of
the
current
study
was
to
map
[
18
F]GSK1482160
for
imaging
purinergic
P2X7R
tauopathy
mouse
models.
MicroPET
performed
using
widely
used
models
(APP/PS1,
5×FAD
3×Tg),
4-repeat
(rTg4510)
mice
age-matched
wild-type
mice.
Increased
uptake
observed
cortex
basal
forebrain
7-month-old
rTg4510
compared
3-month-old
Nonparametric
Spearman’s
rank
analysis
revealed
a
positive
correlation
between
tau
F]APN-1607
hippocampus
No
significant
differences
were
APP/PS1
(5,
10
months),
(3,
7
months)
or
3×Tg
(10
months).
Immunofluorescence
staining
further
indicated
distribution
P2X7Rs
brains
with
accumulation
inclusion
These
findings
provide
vivo
evidence
increased
model
Язык: Английский
mTOR inhibition alleviated tau phosphorylation-induced mitochondrial impairment, oxidative stress, and cognitive impairment
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 24, 2024
Aim:
Hyperphosphorylated
tau
plays
a
crucial
role
in
the
pathogenesis
of
Alzheimer's
disease
(AD).
Whether
mammalian
target
rapamycin
(mTOR)
directly
interacts
with
Tau
protein
at
Ser214,
Ser356
and
Thr231
is
not
clear.
This
study
aimed
to
investigate
whether
mTOR-regulated
phosphorylation
disrupts
mitochondrial
dynamics
function
rapamycin,
an
mTOR
inhibitor,
can
modulate
levels
attenuate
AD-related
alterations.
Methods:
Adeno-associated
virus
(AAV)
vectors
were
used
intracranially
deliver
TauS214E/T231E/S356E
(Tau3E)
variant
into
2-month-old
C57BL/6
mice.
The
mice
intraperitoneally
administered
inhibitor
for
one
week,
followed
by
assessment
via
Morris
water
maze
test.
Western
blot
analysis,
immunofluorescence
staining,
flow
cytometry
employed
measure
expression
mTOR,
p70S6K,
tau;
dynamics;
reactive
oxygen
species
(ROS)
HT22
cells
mouse
model
overexpressing
Tau3E,
as
well
postmortem
brain
tissues
from
AD
patients.
Results:
p-mTORS2448
colocalized
p-TauSer214,
p-TauSer356,
p-TauThr231
hippocampal
CA3
region
Tau3E
presented
elevated
p-mTOR,
downstream
p-p70S6K,
ROS
production;
fragmentation;
p-TauThr231.
Rapamycin
treatment
partially
mitigated
cognitive
molecular
alterations
Conclusion:
revealed
causal
link
between
Ser356,
p-Thr231
upregulation
impairments
ROS,
dysfunction
function.
Treatment
using
(i.p.)
alleviate
impairment,
reduce
p-Tau
restore
homeostasis,
neuronal
loss
impairment
Язык: Английский