Cell,
Journal Year:
2023,
Volume and Issue:
186(17), P. 3706 - 3725.e29
Published: Aug. 1, 2023
The
bone
marrow
in
the
skull
is
important
for
shaping
immune
responses
brain
and
meninges,
but
its
molecular
makeup
among
bones
relevance
human
diseases
remain
unclear.
Here,
we
show
that
mouse
has
most
distinct
transcriptomic
profile
compared
with
other
states
of
health
injury,
characterized
by
a
late-stage
neutrophil
phenotype.
In
humans,
proteome
analysis
reveals
distinct,
differentially
expressed
neutrophil-related
pathways
unique
synaptic
protein
signature.
3D
imaging
demonstrates
structural
cellular
details
skull-meninges
connections
(SMCs)
veins.
Last,
using
translocator
positron
emission
tomography
(TSPO-PET)
imaging,
reflects
inflammatory
disease-specific
spatial
distribution
patients
various
neurological
disorders.
anatomical
functional
potential
as
site
diagnosing,
monitoring,
treating
diseases.
Cell,
Journal Year:
2022,
Volume and Issue:
185(14), P. 2452 - 2468.e16
Published: June 13, 2022
COVID
survivors
frequently
experience
lingering
neurological
symptoms
that
resemble
cancer-therapy-related
cognitive
impairment,
a
syndrome
for
which
white
matter
microglial
reactivity
and
consequent
neural
dysregulation
is
central.
Here,
we
explored
the
neurobiological
effects
of
respiratory
SARS-CoV-2
infection
found
white-matter-selective
in
mice
humans.
Following
mild
mice,
persistently
impaired
hippocampal
neurogenesis,
decreased
oligodendrocytes,
myelin
loss
were
evident
together
with
elevated
CSF
cytokines/chemokines
including
CCL11.
Systemic
CCL11
administration
specifically
caused
neurogenesis.
Concordantly,
humans
lasting
post-COVID
exhibit
levels.
Compared
SARS-CoV-2,
influenza
similar
patterns
reactivity,
oligodendrocyte
loss,
at
early
time
points,
but
after
influenza,
only
pathology
persisted.
These
findings
illustrate
neuropathophysiology
cancer
therapy
may
contribute
to
impairment
following
even
COVID.
Neuron,
Journal Year:
2022,
Volume and Issue:
110(21), P. 3484 - 3496
Published: Oct. 7, 2022
Persistent
neurological
and
neuropsychiatric
symptoms
affect
a
substantial
fraction
of
people
after
COVID-19
represent
major
component
the
post-acute
syndrome,
also
known
as
long
COVID.
Here,
we
review
what
is
understood
about
pathobiology
impact
on
CNS
discuss
possible
neurobiological
underpinnings
cognitive
affecting
survivors.
We
propose
chief
mechanisms
that
may
contribute
to
this
emerging
health
crisis.
Nature,
Journal Year:
2022,
Volume and Issue:
613(7942), P. 120 - 129
Published: Dec. 14, 2022
Abstract
Myelin
is
required
for
the
function
of
neuronal
axons
in
central
nervous
system,
but
mechanisms
that
support
myelin
health
are
unclear.
Although
macrophages
system
have
been
implicated
1
,
it
unknown
which
macrophage
populations
involved
and
aspects
they
influence.
Here
we
show
resident
microglia
crucial
maintenance
adulthood
both
mice
humans.
We
demonstrate
dispensable
developmental
ensheathment.
However,
subsequent
regulation
growth
associated
cognitive
function,
preservation
integrity
by
preventing
its
degeneration.
loss
due
to
absence
with
appearance
a
myelinating
oligodendrocyte
state
altered
lipid
metabolism.
Moreover,
this
mechanism
regulated
through
disruption
TGFβ1–TGFβR1
axis.
Our
findings
highlight
as
promising
therapeutic
targets
conditions
dysregulated,
such
ageing
neurodegenerative
disease
2,3
.
Cell,
Journal Year:
2022,
Volume and Issue:
186(1), P. 194 - 208.e18
Published: Dec. 28, 2022
The
diversity
and
complex
organization
of
cells
in
the
brain
have
hindered
systematic
characterization
age-related
changes
its
cellular
molecular
architecture,
limiting
our
ability
to
understand
mechanisms
underlying
functional
decline
during
aging.
Here,
we
generated
a
high-resolution
cell
atlas
aging
within
frontal
cortex
striatum
using
spatially
resolved
single-cell
transcriptomics
quantified
gene
expression
spatial
major
types
these
regions
over
mouse
lifespan.
We
observed
substantially
more
pronounced
state,
expression,
non-neuronal
neurons.
Our
data
revealed
signatures
glial
immune
activation
aging,
particularly
enriched
subcortical
white
matter,
identified
both
similarities
notable
differences
cell-activation
patterns
induced
by
systemic
inflammatory
challenge.
These
results
provide
critical
insights
into
inflammation
brain.
The Journal of Experimental Medicine,
Journal Year:
2021,
Volume and Issue:
218(9)
Published: July 22, 2021
Alzheimer's
disease
(AD)
is
characterized
by
extracellular
aggregates
of
amyloid
β
peptides,
intraneuronal
tau
aggregates,
and
neuronal
death.
This
pathology
triggers
activation
microglia.
Because
variants
genes
expressed
in
microglia
correlate
with
AD
risk,
microglial
response
to
plausibly
impacts
course.
In
mouse
models,
single-cell
RNA
sequencing
(scRNA-seq)
analyses
delineated
this
as
progressive
conversion
homeostatic
into
disease-associated
(DAM);
additional
reactive
populations
have
been
reported
other
models
neurodegeneration
neuroinflammation.
We
review
all
these
signatures,
highlighting
four
fundamental
patterns:
DAM,
IFN-microglia,
MHC-II
microglia,
proliferating
propose
that
are
either
just
one
or
a
combination,
depending
on
the
clustering
strategy
applied
model.
further
single-nucleus
(snRNA-seq)
data
from
human
specimens
discuss
reasons
for
parallels
discrepancies
between
transcriptional
profiles.
Finally,
we
outline
future
directions
delineating
impact
pathogenesis.
Nature,
Journal Year:
2023,
Volume and Issue:
618(7964), P. 349 - 357
Published: May 31, 2023
The
incidence
of
Alzheimer's
disease
(AD),
the
leading
cause
dementia,
increases
rapidly
with
age,
but
why
age
constitutes
main
risk
factor
is
still
poorly
understood.
Brain
ageing
affects
oligodendrocytes
and
structural
integrity
myelin
sheaths1,
latter
which
associated
secondary
neuroinflammation2,3.
As
support
axonal
energy
metabolism
neuronal
health4-7,
we
hypothesized
that
loss
could
be
an
upstream
for
amyloid-β
(Aβ)
deposition,
central
neuropathological
hallmark
AD.
Here
identify
genetic
pathways
dysfunction
demyelinating
injuries
as
potent
drivers
amyloid
deposition
in
mouse
models
Mechanistically,
causes
accumulation
Aβ-producing
machinery
within
swellings
cleavage
cortical
precursor
protein.
Suprisingly,
AD
mice
dysfunctional
lack
plaque-corralling
microglia
despite
overall
increase
their
numbers.
Bulk
single-cell
transcriptomics
defects
show
there
a
concomitant
induction
highly
similar
distinct
disease-associated
signatures
specific
to
damage
plaques,
respectively.
Despite
successful
induction,
(DAM)
usually
clear
plaques
are
apparently
distracted
nearby
damage.
Our
data
suggest
working
model
whereby
age-dependent
promote
Aβ
plaque
formation
directly
indirectly
therefore
factor.
Improving
oligodendrocyte
health
promising
target
delay
development
slow
progression
