bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Сен. 22, 2023
Summary
Temporally
controlling
cre
recombination
through
tamoxifen
(Tam)
induction
has
many
advantages
for
biomedical
research.
Most
studies
report
Tam
at
early
post-natal/juvenile
(<2
m.o.)
mouse
ages,
but
age-related
neurodegeneration
and
aging
can
require
in
older
mice
(>12
m.o.).
While
anecdotally
reported
as
problematic,
there
are
no
published
comparisons
of
mediated
late
ages.
Here,
microglial-specific
Cx3cr1
creERT
2
were
crossed
to
a
floxed
NuTRAP
reporter
compare
(3-6
(20
Specificity
efficiency
microglial
labeling
21-22
m.o.
identical
induced
with
3-6
or
20
age.
Age-related
translatomic
changes
also
similar
regardless
Each
flox
line
should
be
validated
independently,
however,
these
findings
demonstrate
that
Tam-mediated
performed
even
into
Journal of Neuroinflammation,
Год журнала:
2023,
Номер
20(1)
Опубликована: Авг. 16, 2023
Abstract
Background
Microglia,
the
brain’s
principal
immune
cells,
have
been
implicated
in
pathogenesis
of
Alzheimer’s
disease
(AD),
a
condition
shown
to
affect
more
females
than
males.
Although
sex
differences
microglial
function
and
transcriptomic
programming
described
across
development
models
AD,
no
studies
comprehensively
identified
divergences
that
emerge
aging
mouse
hippocampus.
Further,
existing
AD
generally
develop
pathology
(amyloid
plaques
tau
tangles)
early
life
fail
recapitulate
aged
brain
environment
associated
with
late-onset
AD.
Here,
we
examined
compared
translatomic
effects
young
old
murine
hippocampal
microglia.
Methods
Hippocampal
tissue
from
C57BL6/N
NuTRAP
mice
both
sexes
were
collected
at
(5–6
month-old
[mo])
(22–25
mo)
ages.
Cell
sorting
affinity
purification
techniques
used
isolate
transcriptome
translatome
for
RNA-sequencing
differential
expression
analyses.
Flow
cytometry,
qPCR,
imaging
approaches
confirm
findings.
Results
There
marginal
microglia,
most
differentially
expressed
genes
(DEGs)
restricted
chromosomes.
Both
chromosomally
autosomally
encoded
emerged
aging.
These
DEGs
age
primarily
female-biased
enriched
senescent
disease-associated
signatures.
Normalized
gene
values
can
be
accessed
through
searchable
web
interface
(
https://neuroepigenomics.omrf.org/
).
Pathway
analyses
upstream
regulators
induced
greater
extent
males,
including
inflammatory
mediators
IFNG,
TNF,
IL1B,
as
well
AD-risk
TREM2
APP.
Conclusions
data
suggest
female
microglia
adopt
phenotypes
hippocampus,
even
absence
pathology,
This
sexually
divergent
phenotype
may
explain
difference
susceptibility
progression
case
pathology.
Future
will
need
explore
heterogeneity
response
determine
how
sex-specific
(i.e.,
chromosomal
or
hormonal)
elicit
these
effects.
Abstract
Neuroinflammation
is
closely
linked
to
aging,
which
damages
the
structure
and
function
of
brain.
It
caused
by
intricate
interactions
immune
cells
in
aged
brain,
such
as
dysregulated
glial
dysfunctional
astrocytes.
Aging-associated
chronic
low
inflammation,
referred
neuroinflammaging,
shows
an
upregulated
proinflammatory
response.
Autophagy
senescence
play
crucial
roles
moderators
aging
neuroinflammatory
responses.
The
neuroimmune
system,
dystrophic
cells,
release
factors
alter
blood-brain
barrier,
causing
a
landscape.
Chronic
inflammation
combined
with
deteriorating
neurons
exacerbate
neurological
disorders
decline
cognitive
function.
This
review
highlights
neuroinflammaging
mechanism
associated
interplay
central
nervous
system
cellular
senescence,
autophagy
regulation
brain's
under
conditions.
Moreover,
microglia
peripheral
process
brain
have
also
been
discussed.
Determining
treatment
targets
comprehending
mechanisms
that
influence
necessary
decrease
neuroinflammation.
Molecular Metabolism,
Год журнала:
2024,
Номер
87, С. 101990 - 101990
Опубликована: Июль 14, 2024
This
study
aimed
to
evaluate
the
efficacy
of
a
purification
method
developed
for
isolating
alpha,
beta,
and
delta
cells
from
pancreatic
islets
adult
mice,
extending
its
application
newborn
aged
mice.
Furthermore,
it
sought
examine
transcriptome
dynamics
in
mouse
endocrine
islet
throughout
postnatal
development
validate
age-related
alterations
within
these
cell
populations.
iScience,
Год журнала:
2024,
Номер
27(6), С. 110006 - 110006
Опубликована: Май 16, 2024
Apolipoprotein
E
(apoE)
plays
a
crucial
role
in
the
pathogenesis
of
Alzheimer's
disease
(AD).
Microglia
exhibit
substantial
upregulation
apoE
AD-associated
circumstances,
despite
astrocytes
being
primary
source
expression
and
secretion
brain.
Although
astrocytic
brain
has
been
extensively
investigated,
it
remains
unclear
that
whether
how
particles
generated
from
microglia
differ
biological
characteristic
function.
Here,
we
demonstrate
differences
size
between
astrocytes.
Microglial
impair
neurite
growth
synapses,
promote
neuronal
senescence,
whereas
depletion
GPNMB
(glycoprotein
non-metastatic
melanoma
protein
B)
microglial
mitigated
these
deleterious
effects.
In
addition,
human
APOE4-expressing
are
more
neurotoxic
than
APOE3-bearing
microglia.
For
first
time,
results
offer
concrete
evidence
produced
by
involved
senescence
toxicity.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Март 10, 2023
Microglia,
the
brain's
principal
immune
cells,
have
been
implicated
in
pathogenesis
of
Alzheimer's
disease
(AD),
a
condition
shown
to
affect
more
females
than
males.
Although
sex
differences
microglial
function
and
transcriptomic
programming
described
across
development
models
AD,
no
studies
comprehensively
identified
divergences
that
emerge
aging
mouse
hippocampus.
Further,
existing
AD
generally
develop
pathology
(amyloid
plaques
tau
tangles)
early
life
fail
recapitulate
aged
brain
environment
associated
with
late-onset
AD.
Here,
we
examined
compared
translatomic
effects
young
old
murine
hippocampal
microglia.
