npj Metabolic Health and Disease,
Год журнала:
2024,
Номер
2(1)
Опубликована: Ноя. 8, 2024
Energy
flow
within
cellular
elements
of
the
brain
is
a
well-orchestrated,
tightly
regulated
process,
however,
details
underlying
these
functions
at
single-cell
level
are
still
poorly
understood.
Studying
hypometabolism
in
aging
and
neurodegenerative
diseases
may
benefit
from
experimentation
on
unicellular
bioenergetics.
Here,
we
examined
energy
status
neurons
astrocytes
using
mixed
hippocampal
cultures
PercevalHR,
an
ATP:ADP
nanosensor.
We
assessed
exposures
several
compounds
including
KCl,
glutamate,
FCCP,
insulin,
glucose.
A
mitochondrial
stress
test
was
performed,
PercevalHR's
fluorescence
corrected
for
pH
pHrodo.
Results
demonstrate
that
PercevalHR
can
reliably
report
energetic
two
cell
types
communicate
mixed-culture
setting.
While
FCCP
showed
clear
changes
fluorescence,
insulin
glucose
responses
were
found
to
be
more
subtle
sensitive
extracellular
These
results
highlight
mechanisms
mediate
sensitivity
brain.
Acta Physiologica,
Год журнала:
2025,
Номер
241(2)
Опубликована: Янв. 16, 2025
The
blood-brain
barrier
(BBB)
is
a
highly
selective,
semipermeable
critical
for
maintaining
brain
homeostasis.
BBB
regulates
the
transport
of
essential
nutrients,
hormones,
and
signaling
molecules
between
bloodstream
central
nervous
system
(CNS),
while
simultaneously
protecting
from
potentially
harmful
substances
pathogens.
This
selective
permeability
ensures
that
nourished
shielded
toxins.
An
exception
to
this
are
regions,
such
as
hypothalamus
circumventricular
organs,
which
irrigated
by
fenestrated
capillaries,
allowing
rapid
direct
response
various
blood
components.
We
overview
metabolic
functions
BBB,
with
an
emphasis
on
impact
altered
glucose
metabolism
insulin
in
pathogenesis
neurodegenerative
diseases.
Notably,
endothelial
cells
constituting
exhibit
distinct
characteristics,
primarily
generating
ATP
through
aerobic
glycolysis.
occurs
despite
their
exposure
abundant
oxygen
bloodstream,
typically
supports
oxidative
phosphorylation.
effects
astrocytes,
form
glial
limitans
component
show
marked
sexual
dimorphism.
nutrient
sensing
hypothalamus,
along
signaling,
systemic
metabolism.
Insulin
modifies
regulating
expression
tight
junction
proteins,
angiogenesis,
vascular
remodeling,
well
modulating
flow
brain.
disruptions
particularly
evident
diseases,
Alzheimer's
disease
Parkinson's
disease,
where
breakdown
accelerates
cognitive
decline.
review
highlights
role
normal
functionality
investigates
how
these
pathways
contribute
onset
progression
The
retina
consumes
massive
amounts
of
energy,
yet
its
metabolism
and
substrate
exploitation
remain
poorly
understood.
Here,
we
used
a
murine
explant
model
to
manipulate
retinal
energy
under
entirely
controlled
conditions
utilised
1
H-NMR
spectroscopy-based
metabolomics,
in
situ
enzyme
detection,
cell
viability
readouts
uncover
the
pathways
production.
Our
experimental
manipulations
resulted
varying
degrees
photoreceptor
degeneration,
while
inner
pigment
epithelium
were
essentially
unaffected.
This
selective
vulnerability
photoreceptors
suggested
very
specific
adaptations
their
metabolism.
Rod
found
rely
strongly
on
oxidative
phosphorylation,
but
only
mildly
glycolysis.
Conversely,
cone
dependent
glycolysis
insensitive
electron
transport
chain
decoupling.
Importantly,
appeared
uncouple
glycolytic
Krebs-cycle
via
three
different
pathways:
(1)
mini-Krebs-cycle,
fuelled
by
glutamine
branched
amino
acids,
generating
N
-acetylaspartate;
(2)
alanine-generating
Cahill-cycle;
(3)
lactate-releasing
Cori-cycle.
Moreover,
metabolomics
data
indicated
shuttling
taurine
hypotaurine
between
photoreceptors,
likely
resulting
an
additional
net
transfer
reducing
power
photoreceptors.
These
findings
expand
our
understanding
physiology
pathology
shed
new
light
neuronal
homeostasis
pathogenesis
neurodegenerative
diseases.
Stem Cells Translational Medicine,
Год журнала:
2024,
Номер
13(6), С. 505 - 514
Опубликована: Апрель 8, 2024
Neurological
conditions
conquer
the
world;
they
are
leading
cause
of
disability
and
second
death
worldwide,
appear
all
around
world
in
every
age
group,
gender,
nationality,
socioeconomic
class.
Despite
growing
evidence
an
immense
impact
perturbations
neuroenergetics
on
overall
brain
function,
only
little
is
known
about
underlying
mechanisms.
Especially
human
insights
sparse,
owing
to
a
shortage
physiologically
relevant
model
systems.
With
this
perspective,
we
aim
explore
key
steps
considerations
involved
developing
advanced
vitro
for
studying
neuroenergetics.
We
discuss
biological
technological
strategies
meet
requirements
predictive
model,
aiming
at
providing
guide
inspiration
future
models
The
retina
consumes
massive
amounts
of
energy,
yet
its
metabolism
and
substrate
exploitation
remain
poorly
understood.
Here,
we
used
a
murine
explant
model
to
manipulate
retinal
energy
under
entirely
controlled
conditions
utilized
1
H-NMR
spectroscopy-based
metabolomics,
in
situenzyme
detection,
cell
viability
readouts
uncover
the
pathways
production.
Our
experimental
manipulations
resulted
varying
degrees
photoreceptor
degeneration,
while
inner
pigment
epithelium
were
essentially
unaffected.
This
selective
vulnerability
photoreceptors
suggested
very
specific
adaptations
their
metabolism.
Rod
found
rely
strongly
on
oxidative
phosphorylation,
but
only
mildly
glycolysis.
Conversely,
cone
dependent
glycolysis
insensitive
electron
transport
chain
decoupling.
Importantly,
appeared
uncouple
glycolytic
Krebs-cycle
via
three
different
pathways:
1)
mini-Krebs-cycle,
fueled
by
glutamine
branched-chain
amino
acids,
generating
N-acetylaspartate;
2)
alanine-generating
Cahill-cycle;
3)
lactate-releasing
Cori-cycle.
Moreover,
metabolomic
data
indicated
shuttling
taurine
hypotaurine
between
photoreceptors,
likely
resulting
an
additional
net
transfer
reducing
power
photoreceptors.
These
findings
expand
our
understanding
physiology
pathology
shed
new
light
neuronal
homeostasis
pathogenesis
neurodegenerative
diseases.
Neurology International,
Год журнала:
2024,
Номер
16(3), С. 533 - 550
Опубликована: Май 9, 2024
It
is
well
known
that
the
brain
quite
vulnerable
to
oxidative
stress,
initiating
neuronal
loss
after
ischemia-reperfusion
(IR)
injury.
A
potent
protective
mechanism
ischemic
preconditioning
(IPC),
where
proteins
are
among
primary
targets.
This
study
explores
redox-active
proteins'
role
in
preserving
energy
supply.
Adult
rats
were
divided
into
control,
IR,
and
IPC
groups.
Protein
profiling
was
conducted
identify
modified
then
verified
through
activity
assays,
immunoblot,
immunohistochemical
analyses.
protected
cortex
mitochondria,
as
evidenced
by
a
2.26-fold
increase
superoxide
dismutase
(SOD)
activity.
Additionally,
stable
core
subunits
of
respiratory
chain
complexes
ensured
sufficient
production,
supported
16.6%
ATP
synthase
In
hippocampal
cells,
led
downregulation
energy-related
dehydrogenases,
while
significantly
higher
level
peroxiredoxin
6
(PRX6)
observed.
Notably,
enhanced
glutathione
reductase
provide
maintain
PRX6
function.
Astrocytes
may
mobilize
protect
neurons
during
initial
events,
decreased
positivity
astrocytes,
accompanied
an
following
both
IR
injury
IPC.
Maintained
redox
signaling
via
astrocyte-neuron
communication
triggers
IPC's
state.
The
partnership
PRX6,
SOD,
appears
essential
safeguarding
stabilizing
hippocampus.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 9, 2024
Brain
metabolism
is
essential
for
the
function
of
organisms.
While
established
imaging
methods
provide
valuable
insights
into
brain
metabolic
function,
they
lack
resolution
to
capture
important
interactions
and
heterogeneity
at
cellular
level.
Label-free,
two-photon
excited
fluorescence
addresses
this
issue
by
enabling
dynamic
assessments
single-cell
level
without
manipulations.
In
study,
we
demonstrate
impact
spectral
on
development
rigorous
intensity
lifetime
label-free
protocols
assess
dynamically
over
time
in
3D
engineered
tissue
models
comprising
human
induced
neural
stem
cells,
astrocytes,
microglia.
Specifically,
rely
multi-wavelength
identify
excitation/emission
profiles
key
fluorophores
within
including
NAD(P)H,
LipDH,
FAD,
lipofuscin.
These
enable
mitigate
lipofuscin's
overlap
with
NAD(P)H
flavin
autofluorescence
extract
reliable
optical
metrics
from
images
acquired
two
excitation
wavelengths
emission
bands.
We
present
reporting
redox
state,
mitochondrial
fragmentation,
binding
status
neuronal
monoculture
triculture
systems,
highlight
functional
between
different
cell
types.
Our
findings
reveal
significant
differences
neurons
glial
shedding
light
pathway
utilization,
glutathione
pathway,
OXPHOS,
glycolysis,
fatty
acid
oxidation.
Collectively,
our
studies
establish
a
label-free,
non-destructive
approach
among
types
relying
endogenous
illustrate
complementary
nature
information
that
gained
combining
lifetime-based
images.
Such
can
improve
understanding
physiological
dysfunction
occurs
onset
cancers,
traumatic
injuries
neurodegenerative
diseases.
Journal of Neurochemistry,
Год журнала:
2024,
Номер
169(1)
Опубликована: Авг. 22, 2024
Astrocytes
constitute
a
heterogeneous
cell
population
within
the
brain,
contributing
crucially
to
brain
homeostasis
and
playing
an
important
role
in
overall
function.
Their
function
metabolism
are
not
only
regulated
by
local
signals,
for
example,
from
nearby
neurons,
but
also
long-range
signals
such
as
hormones.
Thus,
two
prominent
hormones
primarily
known
regulating
energy
balance
of
whole
organism,
insulin,
leptin,
have
been
reported
impact
astrocytes
brain.
In
this
study,
we
investigated
acute
regulation
astrocytic
these
cultured
prepared
mouse
cortex
hypothalamus,
pivotal
region
context
nutritional
regulation.
Utilizing
genetically
encoded,
fluorescent
nanosensors,
cytosolic
concentrations
glucose,
lactate,
ATP,
along
with
glycolytic
rate
NADH/NAD
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Июнь 21, 2022
Abstract
The
retina
consumes
massive
amounts
of
energy,
yet
its
metabolism
and
substrate
exploitation
remain
poorly
understood.
Here,
we
used
a
murine
explant
model
to
manipulate
retinal
energy
under
entirely
controlled
conditions
utilized
1
H-NMR
spectroscopy-based
metabolomics,
in
situenzyme
detection,
cell
viability
readouts
uncover
the
pathways
production.
Our
experimental
manipulations
resulted
varying
degrees
photoreceptor
degeneration,
while
inner
pigment
epithelium
were
essentially
unaffected.
This
selective
vulnerability
photoreceptors
suggested
very
specific
adaptations
their
metabolism.
Rod
found
rely
strongly
on
oxidative
phosphorylation,
but
only
mildly
glycolysis.
Conversely,
cone
dependent
glycolysis
insensitive
electron
transport
chain
decoupling.
Importantly,
appeared
uncouple
glycolytic
Krebs-cycle
via
three
different
pathways:
1)
mini-Krebs-cycle,
fueled
by
glutamine
branched-chain
amino
acids,
generating
N-acetylaspartate;
2)
alanine-generating
Cahill-cycle;
3)
lactate-releasing
Cori-cycle.
Moreover,
metabolomic
data
indicated
shuttling
taurine
hypotaurine
between
photoreceptors,
likely
resulting
an
additional
net
transfer
reducing
power
photoreceptors.
These
findings
expand
our
understanding
physiology
pathology
shed
new
light
neuronal
homeostasis
pathogenesis
neurodegenerative
diseases.
Graphical
abstract
Retinal
employ
both
glucose
glutamate
as
fuels.
While
rod
phosphorylation
N-acetylaspartate
producing
lactate-producing
Cori
cycle
oxidative,
alanine
Cahill
cycle.
Highlights
utilizes
complex
switchboard
consisting
Krebs
cycle,
mini-Krebs
Mini-Krebs
runs
more
efficiently
than
‘full’
Alanine
transaminase
decouples
from
Lactate,
alanine,
are
distinctive
energetic
pathway
signatures.
The
retina
consumes
massive
amounts
of
energy,
yet
its
metabolism
and
substrate
exploitation
remain
poorly
understood.
Here,
we
used
a
murine
explant
model
to
manipulate
retinal
energy
under
entirely
controlled
conditions
utilised
1
H-NMR
spectroscopy-based
metabolomics,
in
situ
enzyme
detection,
cell
viability
readouts
uncover
the
pathways
production.
Our
experimental
manipulations
resulted
varying
degrees
photoreceptor
degeneration,
while
inner
pigment
epithelium
were
essentially
unaffected.
This
selective
vulnerability
photoreceptors
suggested
very
specific
adaptations
their
metabolism.
Rod
found
rely
strongly
on
oxidative
phosphorylation,
but
only
mildly
glycolysis.
Conversely,
cone
dependent
glycolysis
insensitive
electron
transport
chain
decoupling.
Importantly,
appeared
uncouple
glycolytic
Krebs-cycle
via
three
different
pathways:
(1)
mini-Krebs-cycle,
fuelled
by
glutamine
branched
amino
acids,
generating
N
-acetylaspartate;
(2)
alanine-generating
Cahill-cycle;
(3)
lactate-releasing
Cori-cycle.
Moreover,
metabolomics
data
indicated
shuttling
taurine
hypotaurine
between
photoreceptors,
likely
resulting
an
additional
net
transfer
reducing
power
photoreceptors.
These
findings
expand
our
understanding
physiology
pathology
shed
new
light
neuronal
homeostasis
pathogenesis
neurodegenerative
diseases.