Journal of Neuroscience,
Год журнала:
2020,
Номер
40(39), С. 7559 - 7576
Опубликована: Авг. 31, 2020
Degeneration
of
locus
Coeruleus
(LC)
neurons
and
dysregulation
noradrenergic
signaling
are
ubiquitous
features
Parkinson9s
disease
(PD).
The
LC
is
among
the
first
brain
regions
affected
by
α-synuclein
(asyn)
pathology,
yet
how
asyn
affects
these
remains
unclear.
LC-derived
norepinephrine
(NE)
can
stimulate
neuroprotective
mechanisms
modulate
immune
cells,
while
NE
neurotransmission
may
exacerbate
progression,
particularly
nonmotor
symptoms,
contribute
to
chronic
neuroinflammation
associated
with
PD
pathology.
Although
transgenic
mice
overexpressing
have
previously
been
developed,
transgene
expression
usually
driven
pan-neuronal
promoters
thus
has
not
selectively
targeted
neurons.
Here
we
report
a
novel
mouse
expressing
human
wild-type
under
control
noradrenergic-specific
dopamine
β-hydroxylase
promoter
(DBH-hSNCA).
These
developed
oligomeric
conformation-specific
in
neurons,
alterations
hippocampal
microglial
abundance,
upregulated
GFAP
expression,
degeneration
fibers,
decreased
striatal
DA
metabolism,
age-dependent
behaviors
reminiscent
symptoms
that
were
rescued
adrenergic
receptor
antagonists.
provide
insights
into
pathology
central
dysfunction
early
pathophysiology.
SIGNIFICANCE
STATEMENT
ɑ-Synuclein
loss
two
most
neuropathologic
Dysregulated
PD,
including
sleep
disturbances,
emotional
changes
such
as
anxiety
depression,
cognitive
decline.
Importantly,
inflammation
in,
progression
of,
PD.
We
generated
investigate
increased
function
transmission
behaviors.
cytotoxic
effects
asyn,
astrogliosis,
fiber
degeneration,
disruptions
without
inclusions.
International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
21(22), С. 8630 - 8630
Опубликована: Ноя. 16, 2020
Locus
Coeruleus
(LC)
is
the
main
noradrenergic
nucleus
of
central
nervous
system,
and
its
neurons
widely
innervate
whole
brain.
LC
severely
degenerated
both
in
Alzheimer’s
disease
(AD)
Parkinson’s
(PD),
years
before
onset
clinical
symptoms,
through
mechanisms
that
differ
among
two
disorders.
Several
experimental
studies
have
shown
noradrenaline
modulates
neuroinflammation,
mainly
by
acting
on
microglia/astrocytes
function.
In
present
review,
after
a
brief
introduction
anatomy
physiology
LC,
we
provide
an
overview
data
supporting
pathogenetic
role
degeneration
AD
PD.
Then,
describe
detail
data,
obtained
vitro
vivo
animal
models,
which
support
potential
neuroinflammation
such
link,
specific
molecules
(i.e.,
released
cytokines,
glial
receptors,
including
pattern
recognition
receptors
others)
whose
expression
altered
might
play
key
AD/PD
pathogenesis.
New
imaging
biochemical
tools
recently
been
developed
humans
to
estimate
integrity
degree
pathology
biomarkers;
it
auspicable
these
will
allow
near
future
test
existence
link
between
LC-neuroinflammation
neurodegeneration
directly
patients.
Current Neurology and Neuroscience Reports,
Год журнала:
2020,
Номер
21(1)
Опубликована: Дек. 12, 2020
Locus
coeruleus
(LC)
is
the
main
noradrenergic
nucleus
of
brain,
and
its
degeneration
considered
to
be
key
in
pathogenesis
neurodegenerative
diseases.
In
last
15
years,MRI
has
been
used
assess
LC
vivo,
both
healthy
subjects
patients
suffering
from
neurological
disorders.
this
review,
we
summarize
findings
LC-MRI
studies,
interpreting
them
light
preclinical
histopathological
data,
discussing
potential
role
as
diagnostic
experimental
tool.
Journal of Neuroscience,
Год журнала:
2020,
Номер
40(39), С. 7559 - 7576
Опубликована: Авг. 31, 2020
Degeneration
of
locus
Coeruleus
(LC)
neurons
and
dysregulation
noradrenergic
signaling
are
ubiquitous
features
Parkinson9s
disease
(PD).
The
LC
is
among
the
first
brain
regions
affected
by
α-synuclein
(asyn)
pathology,
yet
how
asyn
affects
these
remains
unclear.
LC-derived
norepinephrine
(NE)
can
stimulate
neuroprotective
mechanisms
modulate
immune
cells,
while
NE
neurotransmission
may
exacerbate
progression,
particularly
nonmotor
symptoms,
contribute
to
chronic
neuroinflammation
associated
with
PD
pathology.
Although
transgenic
mice
overexpressing
have
previously
been
developed,
transgene
expression
usually
driven
pan-neuronal
promoters
thus
has
not
selectively
targeted
neurons.
Here
we
report
a
novel
mouse
expressing
human
wild-type
under
control
noradrenergic-specific
dopamine
β-hydroxylase
promoter
(DBH-hSNCA).
These
developed
oligomeric
conformation-specific
in
neurons,
alterations
hippocampal
microglial
abundance,
upregulated
GFAP
expression,
degeneration
fibers,
decreased
striatal
DA
metabolism,
age-dependent
behaviors
reminiscent
symptoms
that
were
rescued
adrenergic
receptor
antagonists.
provide
insights
into
pathology
central
dysfunction
early
pathophysiology.
SIGNIFICANCE
STATEMENT
ɑ-Synuclein
loss
two
most
neuropathologic
Dysregulated
PD,
including
sleep
disturbances,
emotional
changes
such
as
anxiety
depression,
cognitive
decline.
Importantly,
inflammation
in,
progression
of,
PD.
We
generated
investigate
increased
function
transmission
behaviors.
cytotoxic
effects
asyn,
astrogliosis,
fiber
degeneration,
disruptions
without
inclusions.
