As
a
key
member
of
the
neurotrophin
family
in
central
nervous
system,
brain-derived
neurotrophic
factor
(BDNF)
plays
critical
role
maintenance
and
plasticity
system.
Its
innate
neuroprotective
advantage
can
also
be
shared
with
brain
when
normal
aging-dependent
processes
challenge
neural
circuits.
The
intricate
relationship
between
BDNF
resilience
during
aging
process
signifies
molecular
mechanisms
that
underlie
protection
function,
such
as
cognition,
movement
psychological
well-being.
is
crucial
for
neuronal
growth
survival,
it
promote
against
age-related
functional
decline
frailty,
even
if
fails
to
entirely
prevent
ageing-related
decline.
In
present
review,
we
discuss
function
from
perspective
how
may
aging.
We
emphasize
briefly
principal,
well-known
cellular
hallmarks
restrict
disabling
dynamics
enhance
overall
Insight
into
pathways
through
which
reduces
dysfunctions
and/or
improves
resilience,
provide
foundation
developing
targeted
interventions
mental
well-being
an
population.
CNS Neuroscience & Therapeutics,
Год журнала:
2025,
Номер
31(3)
Опубликована: Март 1, 2025
Neuropathic
pain
(NP)
arises
from
neuroimmune
interactions
following
nerve
injury
and
is
often
accompanied
by
anxiety
depression.
The
aim
of
the
study
to
evaluate
effects
noradrenergic
locus
coeruleus
(LC),
a
key
regulator
emotional
states,
projects
extensively
hippocampus.
We
investigated
chronic
NP
on
LC
integrity
its
projections
hippocampal
CA3
region
in
spared
(SNI)
mice
with
behavioral
tests,
immunohistochemistry,
neurochemical
analyses,
Gq-DREADD.
Chronic
induced
neuronal
loss,
reduced
norepinephrine
(NE)
release,
triggered
microglial
activation
neuroinflammation
CA3.
Selective
LC-CA3
neurons
using
Gq-DREADD
chemogenetics
alleviated
comorbid
anxiety-
depression-like
behaviors.
This
intervention
suppressed
activation,
decreased
proinflammatory
cytokines
(TNF-α
IL-1β),
restored
NE
levels
Our
findings
highlighted
therapeutic
potential
targeting
mitigate
neuropsychiatric
comorbidities
via
modulation
neuroinflammation.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 17, 2025
Abstract
Alzheimer's
disease
(AD),
the
most
prevalent
type
of
dementia,
is
characterized
by
a
biological
process
that
begins
with
development
AD
neuropathologic
change
(ADNPC)
while
individuals
remain
asymptomatic.
A
key
molecular
hallmark
ADNPC
accumulation
amyloid‐β
plaques.
β‐secretase
plays
critical
role
in
upstream
pathological
cleavage
amyloid
precursor
protein
(APP),
producing
peptides
are
prone
to
misfolding,
ultimately
contributing
plaque
formation.
Neuronal
extracellular
vesicles
(NEVs)
blood
transport
and
preserve
its
activity,
allowing
for
noninvasive
profiling
activity
detecting
early
onset
ADNPC.
In
this
study,
novel
approach
approached
assessment
patients
using
an
NEV
assay.
This
assay
identifies
NEVs
exhibiting
colocalization
markers
AD‐associated
β‐secretase,
generating
profile
each
patient.
The
represents
significant
advancement
leveraging
diagnostic
potential
NEVs,
offering
noninvasive,
quantitative
method
reliably
assessing
detect
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 16, 2025
Abstract
Isolated
REM
sleep
behavior
(iRBD)
is
a
male
predominant
parasomnia
characterized
by
abnormal
dream-enacting
movements
in
sleep.
It
the
prodromal
manifestation
most
strongly
associated
with
development
of
synucleinopathies,
such
as
Parkinson’s
disease
or
dementia
Lewy
bodies.
While
individuals
iRBD
exhibit
significant
cortical
atrophy
shaped
distinct
gene
expression,
sex-specific
differences
structural
brain
changes
remain
unknown.
In
this
study,
we
investigate
effect
sex
on
and
examine
expression
underpinning
abnormalities
large
international
multicentric
MRI
dataset
polysomnography-confirmed
iRBD.
T1-weighted
scans
from
408
480
healthy
controls
were
acquired.
Vertex-based
surface
reconstruction
segmentation
conducted,
general
linear
models
used
to
quantify
assess
thickness
compared
controls.
We
then
high
resolution
parcellation
further
characterize
conduct
imaging
transcriptomics
analyses.
Gene
enrichment
analyses
performed
identify
genes
Males
showed
significantly
more
thinning
females
controls,
despite
similar
age
clinical
features.
The
analysis
revealed
that
female-specific
resilience
was
overexpression
oestrogen-related
receptors.
These
findings
provide
mechanistic
insight
neuroprotection
stages
highlighting
critical
impact
progression
neurodegenerative
diseases.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 8, 2024
Abstract
Identifying
readily
implementable
methods
that
can
effectively
counteract
aging
is
urgently
needed
for
tackling
age-related
degenerative
disorders.
Here,
we
conducted
functional
assessments
and
deep
molecular
phenotyping
in
the
mouse
to
demonstrate
glucagon-like
peptide-1
receptor
agonist
(GLP-1RA)
treatment
attenuates
body-wide
changes.
Apart
from
improvements
physical
cognitive
performance,
age-counteracting
effects
are
prominently
evident
at
multiple
omic
levels.
These
span
transcriptomes
DNA
methylomes
of
various
tissues,
organs
circulating
white
blood
cells,
as
well
plasma
metabolome.
Importantly,
beneficial
specific
aged
mice,
not
young
adults,
achieved
with
a
low
dosage
GLP-1RA
which
has
negligible
impact
on
food
consumption
body
weight.
The
rejuvenation
exhibit
organ-specific
characteristics,
generally
heavily
dependent
hypothalamic
GLP-1R.
We
benchmarked
against
those
mTOR
inhibition,
well-established
anti-aging
intervention,
observing
strong
resemblance
across
two
strategies.
Our
findings
have
broad
implications
understanding
mechanistic
basis
clinically
observed
pleiotropic
GLP-1RAs,
design
intervention
trials
diseases,
development
anti-aging-based
therapeutics.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 31, 2024
SUMMARY
In
Alzheimer’s
disease
(AD),
the
microtubule-binding
protein
tau
becomes
abnormally
hyperphosphorylated
and
aggregated
in
selective
brain
regions
such
as
cortex
hippocampus
1–3
.
However,
other
like
cerebellum
stem
remain
largely
intact
despite
universal
expression
of
throughout
brain.
Here,
we
found
that
an
understudied
splice
isoform
termed
“big
tau”
is
significantly
more
abundant
less
vulnerable
to
pathology
compared
pathology-vulnerable
regions.
We
used
various
cellular
animal
models
demonstrate
big
possesses
multiple
properties
can
resist
AD-related
pathological
changes.
Importantly,
human
AD
patients
show
a
higher
level
pathology-resisting
cerebellum,
region
spared
from
pathology.
Our
study
examines
unique
tau,
expanding
our
current
understanding
pathophysiology.
Altogether,
data
suggest
alternative
splicing
favor
viable
strategy
modulate
Aging and Disease,
Год журнала:
2024,
Номер
unknown, С. 0 - 0
Опубликована: Янв. 1, 2024
As
a
key
member
of
the
neurotrophin
family
in
central
nervous
system,
brain-derived
neurotrophic
factor
(BDNF)
plays
critical
role
maintenance
and
plasticity
system.
Its
innate
neuroprotective
advantage
can
also
be
shared
with
brain
when
normal
aging-dependent
processes
challenge
neural
circuits.
The
intricate
relationship
between
BDNF
resilience
during
aging
process
signifies
molecular
mechanisms
that
underlie
protection
function,
such
as
cognition,
movement
psychological
well-being.
is
crucial
for
neuronal
growth
survival,
it
promote
against
age-related
functional
decline
frailty,
even
if
fails
to
entirely
prevent
aging-related
decline.
In
present
review,
we
discuss
function
from
perspective
how
may
aging.
We
emphasize
briefly
principal,
well-known
cellular
hallmarks
restrict
disabling
dynamics
enhance
overall
Insight
into
pathways
through
which
reduces
dysfunctions
and/or
improves
resilience,
provides
foundation
developing
targeted
interventions
mental
well-being
an
population.
