Environmental Science & Technology,
Journal Year:
2021,
Volume and Issue:
55(11), P. 7501 - 7509
Published: May 19, 2021
Manganese
(Mn)
is
an
essential
nutrient
for
metabolic
functions,
yet
excessive
exposure
can
lead
to
neurological
disease
in
adults
and
neurodevelopmental
deficits
children.
Drinking
water
represents
one
of
the
routes
Mn
exposure.
Both
natural
enrichment
from
rocks
soil,
man-made
contamination
pollute
groundwater
that
supplies
drinking
a
substantial
fraction
U.S.
population.
Conventional
methods
monitoring
are
costly
involve
long
turn-around
time.
Recent
advancements
electrochemical
sensing,
however,
have
led
development
miniature
sensors
determination.
These
rely
on
cathodic
stripping
voltammetry
electroanalytical
technique
miniaturized
platinum
working
electrode.
In
this
study,
we
validate
these
determination
concentrations
against
standard
method
using
inductively
coupled
plasma
mass
spectrometry
(ICP-MS).
samples
(n
=
78)
0.03
ppb
5.3
ppm
range
were
analyzed.
Comparisons
with
ICP-MS
yielded
100%
agreement,
∼70%
accuracy,
∼91%
precision.
We
envision
use
our
system
rapid
inexpensive
point-of-use
identification
levels
water,
which
especially
valuable
frequent
where
present.
Molecular Neurodegeneration,
Journal Year:
2024,
Volume and Issue:
19(1)
Published: March 19, 2024
Abstract
Background
Dynamin-related
protein
1
(Drp1)
plays
a
critical
role
in
mitochondrial
dynamics.
Partial
inhibition
of
this
is
protective
experimental
models
neurological
disorders
such
as
Parkinson’s
disease
and
Alzheimer’s
disease.
The
mechanism
has
been
attributed
primarily
to
improved
function.
However,
the
observations
that
Drp1
reduces
aggregation
suggest
involvement
autophagy.
To
investigate
potential
novel
inhibition,
model
with
impaired
autophagy
without
needed.
Methods
We
characterized
effects
manganese
(Mn),
which
causes
parkinsonian-like
symptoms
humans,
on
mitochondria
by
performing
dose-response
studies
two
cell
culture
(stable
HeLa
reporter
cells
N27
rat
immortalized
dopamine
neuronal
cells).
Mitochondrial
function
was
assessed
using
Seahorse
Flux
Analyzer.
Autophagy
flux
monitored
quantifying
number
autophagosomes
autolysosomes,
well
levels
other
proteins.
strengthen
vitro
data,
multiple
mouse
(autophagy
mice
mutant
+/−
their
wild-type
littermates)
were
orally
treated
low
chronic
Mn
regimen
previously
reported
increase
α-synuclein
transmission
via
exosomes.
RNAseq,
laser
captured
microdissection,
immunofluorescence,
immunoblotting,
stereological
counting,
behavioural
used.
Results
data
demonstrate
at
non-toxic
concentrations,
but
not
morphology.
In
midbrain,
RNAseq
further
confirmed
pathways
dysregulated
related
genes.
Additionally,
selectively
nigral
neurons
nearby
GABA
neurons.
partial
Drp1-knockdown
mice,
induced
autophagic
impairment
significantly
prevented.
Consistent
these
observations,
increased
proteinase-K
resistant
protected
against
pathology.
Conclusions
This
study
demonstrates
separate
conferred
independent
its
fission.
Given
dysfunction
are
prominent
features
neurodegenerative
diseases,
combined
mechanisms
targeting
make
an
attractive
therapeutic
target.
Graphical
Acta Neuropathologica Communications,
Journal Year:
2019,
Volume and Issue:
7(1)
Published: Nov. 19, 2019
Abstract
Targeting
alpha-synuclein
(α-syn)
as
a
therapeutic
strategy
for
Parkinson’s
disease
(PD)
has
been
intensively
pursued
largely
due
to
its
well-recognized
pathogenic
role.
Since
discovery
the
first
familial
link
PD
over
two
decades
ago,
this
protein
associated
with
multiple
neurotoxic
mechanisms,
such
mitochondrial
dysfunction
and
impaired
autophagic
flux.
We
report
here
that
blocking
dynamin-related
1
(Drp1)
improved
both
function
flux
in
experimental
models
of
α-syn.
Using
rat
dopaminergic
neuronal
cells
inducible
wild-type
human
α-syn,
we
observed
excessive
fragmentation
increased
Drp1
levels
48
h
after
gene
induction.
Functionally,
these
exhibited
lower
membrane
potential,
reduced
ATP
production
rate
spare
respiratory
capacity,
well
reactive
oxygen
species.
To
evaluate
protective
role
inhibition,
used
three
complementary
approaches:
silencing
mediated
by
siRNA,
overexpression
Drp1-dominant
negative
small
molecule
division
inhibitor-1
(mdivi-1).
Both
morphological
functional
defects
induced
α-syn
were
attenuated
strategies.
Importantly,
inhibition
proteinase
K-resistant
aggregates.
Based
on
observation,
investigated
involvement
autophagy.
Through
combination
stable
autophagy
reporter
immunoreactivity
LC3
p62
either
or
treatment
preformed
fibrils
(PFF),
abolished
impairment
Consistent
improving
function,
exosome
release
spread
pathology
from
neurons
microglia
neurons.
In
summary,
study
highlights
new
insights
confers
neuroprotection
through
autophagy-lysosomal
pathways,
further
strengthening
potential
targeting
Drp1.
Translational Psychiatry,
Journal Year:
2020,
Volume and Issue:
10(1)
Published: July 7, 2020
Abstract
Neurodevelopmental
regression
(NDR)
is
a
subtype
of
autism
spectrum
disorder
(ASD)
that
manifests
as
loss
previously
acquired
developmental
milestones.
Early
life
dysregulation
nutritional
metals
and/or
exposure
to
toxic
have
been
associated
with
ASD,
but
the
underlying
biological
mechanisms
by
which
influence
neurodevelopment
remain
unclear.
We
hypothesize
influences
through
bioenergetics.
Prenatal
and
early
postnatal
metal
exposures
were
measured
using
validated
tooth-matrix
biomarkers
in
27
ASD
cases
(13
NDR)
7
typically-developing
(TD)
controls.
Mitochondrial
respiration
glycolysis
peripheral
blood
mononuclear
cells
Seahorse
XF96.
Children
demonstrated
lower
prenatal
Copper
(Cu)
Nickel
concentrations
Copper-to-Zinc
(Cu/Zn)
ratio
compared
TD
children.
NDR
showed
greater
metal-related
disruption
cellular
bioenergetics
than
children
without
NDR.
For
mitochondrial
decreased
Manganese
concentration
increased
Zinc
increased;
Lead
Manganese.
history
NDR,
Tin.
Language
communication
scores
positively
related
Cu
Cu/Zn
ratio.
This
study
suggests
may
be
important
for
differences
bioenergetics,
particularly
ASD.
Environmental Science & Technology,
Journal Year:
2021,
Volume and Issue:
55(11), P. 7501 - 7509
Published: May 19, 2021
Manganese
(Mn)
is
an
essential
nutrient
for
metabolic
functions,
yet
excessive
exposure
can
lead
to
neurological
disease
in
adults
and
neurodevelopmental
deficits
children.
Drinking
water
represents
one
of
the
routes
Mn
exposure.
Both
natural
enrichment
from
rocks
soil,
man-made
contamination
pollute
groundwater
that
supplies
drinking
a
substantial
fraction
U.S.
population.
Conventional
methods
monitoring
are
costly
involve
long
turn-around
time.
Recent
advancements
electrochemical
sensing,
however,
have
led
development
miniature
sensors
determination.
These
rely
on
cathodic
stripping
voltammetry
electroanalytical
technique
miniaturized
platinum
working
electrode.
In
this
study,
we
validate
these
determination
concentrations
against
standard
method
using
inductively
coupled
plasma
mass
spectrometry
(ICP-MS).
samples
(n
=
78)
0.03
ppb
5.3
ppm
range
were
analyzed.
Comparisons
with
ICP-MS
yielded
100%
agreement,
∼70%
accuracy,
∼91%
precision.
We
envision
use
our
system
rapid
inexpensive
point-of-use
identification
levels
water,
which
especially
valuable
frequent
where
present.
