Successful
neurogenesis
requires
adequate
proliferation
of
neural
stem
cells
(NSCs)
and
their
progeny,
followed
by
neuronal
differentiation,
maturation
survival.
NSCs
inhabit
a
complex
cellular
microenvironment,
the
niche,
which
influences
behaviour.
To
ensure
sustained
neurogenesis,
niche
must
respond
to
extrinsic,
environmental
changes
whilst
fulfilling
intrinsic
requirements
neurogenic
program
adapting
roles
accordingly.
However,
very
little
is
known
about
how
different
adjust
properties
such
inputs.
Here,
we
show
that
nutritional
NSC-derived
signals
induce
remodelling
Drosophila
cortex
glia,
this
glial
evolving
needs
NSCs.
First,
nutrition-induced
activation
PI3K/Akt
drives
glia
expand
membrane
processes.
Second,
when
emerge
from
quiescence
resume
proliferation,
they
signal
promote
formation
bespoke
structure
around
each
NSC
lineage.
The
remodelled
essential
for
newborn
neuron
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Фев. 19, 2024
Introduction
The
goal
of
this
study
is
to
explore
the
pharmacological
potential
amyloid-reducing
vasodilator
fasudil,
a
selective
Ras
homolog
(Rho)-associated
kinases
(ROCK)
inhibitor,
in
P301S
tau
transgenic
mouse
model
(Line
PS19)
neurodegenerative
tauopathy
and
Alzheimer's
disease
(AD).
Methods
We
used
LC-MS/MS,
ELISA
bioinformatic
approaches
investigate
effect
treatment
with
fasudil
on
brain
proteomic
profile
PS19
mice.
also
explored
efficacy
reducing
phosphorylation,
beneficial
and/or
toxic
effects
its
administration
Results
Proteomic
profiling
mice
brains
exposed
revealed
activation
mitochondrial
tricarboxylic
acid
(TCA)
cycle
blood-brain
barrier
(BBB)
gap
junction
metabolic
pathways.
observed
significant
negative
correlation
between
levels
phosphorylated
(pTau)
at
residue
396
both
metabolite
hydroxyfasudil.
Conclusions
Our
results
provide
evidence
proteins
pathways
related
mitochondria
BBB
functions
by
support
further
development
therapeutic
for
AD.
Abstract
While
calcium
signaling
in
excitable
cells,
such
as
muscle
or
neurons,
is
extensively
characterized,
epithelial
tissues
little
understood.
Specifically,
the
range
of
intercellular
patterns
elicited
by
tightly
coupled
cells
and
their
function
regulation
characteristics
are
explored.
We
found
that
Drosophila
imaginal
discs,
a
widely
studied
model
organ,
complex
spatiotemporal
dynamics
occur.
describe
include
waves
traversing
large
tissue
domains
striking
oscillatory
well
spikes
confined
to
local
neighboring
cells.
The
oscillations
arise
emergent
properties
mobilization
within
sheet
gap-junction
influenced
cell
size
environmental
history.
vivo
spikes,
requires
further
characterization,
our
genetic
experiments
suggest
core
components
guide
actomyosin
organization.
Our
study
thus
suggests
possible
role
for
epithelia
but
importantly,
introduces
epithelium
enabling
dissection
cellular
mechanisms
supporting
initiation,
transmission
regeneration
long-range
emergence
highly
multicellular
sheet.
Successful
neurogenesis
requires
adequate
proliferation
of
neural
stem
cells
(NSCs)
and
their
progeny,
followed
by
neuronal
differentiation,
maturation
survival.
NSCs
inhabit
a
complex
cellular
microenvironment,
the
niche,
which
influences
behaviour.
To
ensure
sustained
neurogenesis,
niche
must
respond
to
extrinsic,
environmental
changes
whilst
fulfilling
intrinsic
requirements
neurogenic
program
adapting
roles
accordingly.
However,
very
little
is
known
about
how
different
adjust
properties
such
inputs.
Here,
we
show
that
nutritional
NSC-derived
signals
induce
remodelling
Drosophila
cortex
glia,
this
glial
evolving
needs
NSCs.
First,
nutrition-induced
activation
PI3K/Akt
drives
glia
expand
membrane
processes.
Second,
when
emerge
from
quiescence
resume
proliferation,
they
signal
promote
formation
bespoke
structure
around
each
NSC
lineage.
The
remodelled
essential
for
newborn
neuron
