Frontiers in Neuroscience,
Journal Year:
2020,
Volume and Issue:
14
Published: Oct. 6, 2020
The
locus
coeruleus
(LC)
has
long
been
underappreciated
for
its
role
in
the
pathophysiology
of
Alzheimer's
disease
(AD),
Parkinson's
(PD),
and
other
neurodegenerative
disorders.
While
AD
PD
are
distinct
clinical
presentation,
both
characterized
by
prodromal
protein
aggregation
LC,
late-stage
degeneration
comorbid
conditions
indicative
LC
dysfunction.
Many
these
early
studies
were
limited
to
post-mortem
histological
techniques
due
LC's
small
size
location
deep
brainstem.
Thus,
there
is
a
growing
interest
utilizing
vivo
imaging
as
predictor
preclinical
processes
biomarker
progression.
Simultaneously,
neuroimaging
animal
models
holds
promise
identifying
alterations
circuits,
but
thus
far
underutilized.
still
infancy,
handful
have
reported
effects
single
gene
mutations
pathology
on
function
using
various
techniques.
Furthermore,
combining
optogenetics
or
chemogenetics
allows
interrogation
network
connectivity
response
changes
activity.
purpose
this
article
twofold:
(1)
review
what
magnetic
resonance
(MRI)
positron
emission
tomography
(PET)
revealed
about
dysfunction
potential
humans,
(2)
explore
how
can
be
used
test
hypotheses
derived
from
data
establish
mechanistic
framework
inform
LC-focused
therapeutic
interventions
alleviate
symptoms
impede
Clinical and Translational Medicine,
Journal Year:
2021,
Volume and Issue:
11(4)
Published: April 1, 2021
Alzheimer's
disease
(AD)
poses
a
significant
global
health
concern
over
the
next
several
decades.
Multiple
hypotheses
have
been
put
forth
that
attempt
to
explain
underlying
pathophysiology
of
AD.
Many
these
are
briefly
reviewed
here,
but
to-date
no
disease-altering
therapy
has
achieved.
Despite
this,
recent
work
expanding
on
role
noradrenergic
system
dysfunction
in
both
pathogenesis
and
symptomatic
exacerbation
AD
shown
promise.
The
norepinephrine
(NE)
plays
remains
complicated
pre-tangle
tau
consistently
arise
locus
coeruleus
(LC)
patients
with
decades
before
symptom
onset.
current
research
here
indicates
NE
can
facilitate
neuroprotective
memory-enhancing
effects
through
β
adrenergic
receptors,
while
α
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(11), P. 6143 - 6143
Published: May 30, 2022
A
growing
body
of
evidence
demonstrates
the
important
role
noradrenergic
system
in
pathogenesis
many
neurodegenerative
processes,
especially
Alzheimer’s
disease,
due
to
its
ability
control
glial
activation
and
chemokine
production
resulting
anti-inflammatory
neuroprotective
effects.
Noradrenaline
involvement
this
disease
was
first
proposed
after
finding
deficits
neurons
locus
coeruleus
from
patients.
Based
on
this,
it
has
been
hypothesized
that
early
loss
projections
subsequent
reduction
noradrenaline
brain
levels
contribute
cognitive
dysfunctions
progression
neurodegeneration.
Several
studies
have
focused
analyzing
development
disease.
In
review
we
summarize
some
most
relevant
data
describing
alterations
normally
occurring
as
well
experimental
which
concentration
modified
order
further
analyze
how
these
affect
behavior
viability
different
nervous
cells.
The
combination
here
presented
suggests
maintenance
adequate
central
constitutes
a
key
factor
endogenous
defense
systems
help
prevent
or
delay
For
reason,
use
modulating
drugs
is
an
interesting
alternative
therapeutic
option
for
Journal of Alzheimer s Disease,
Journal Year:
2022,
Volume and Issue:
86(3), P. 1037 - 1059
Published: Feb. 11, 2022
Background:
The
locus
coeruleus
(LC)
is
one
of
the
earliest
brain
regions
to
accumulate
hyperphosphorylated
tau,
but
a
lack
animal
models
that
recapitulate
this
pathology
has
hampered
our
understanding
its
contributions
Alzheimer’s
disease
(AD)
pathophysiology.
Objective:
We
previously
reported
TgF344-AD
rats,
which
overexpress
mutant
human
amyloid
precursor
protein
and
presenilin-1,
early
endogenous
tau
in
LC.
Here,
we
used
rats
wild-type
(WT)
virus
interrogate
effects
rat
LC
on
AD-related
neuropathology
behavior.
Methods:
Two-month-old
WT
received
bilateral
infusions
full-length
or
mCherry
control
driven
by
noradrenergic-specific
PRSx8
promoter.
Rats
were
subsequently
assessed
at
6
12
months
for
arousal
(sleep
latency),
anxiety-like
behavior
(open
field,
elevated
plus
maze,
novelty-suppressed
feeding),
passive
coping
(forced
swim
task),
learning
memory
(Morris
water
maze
fear
conditioning).
Hippocampal
microglia,
astrocyte,
AD
evaluated
using
immunohistochemistry.
Results:
In
general,
age
more
pronounced
than
genotype
treatment;
older
displayed
greater
hippocampal
pathology,
took
longer
fall
asleep,
had
reduced
locomotor
activity,
floated
more,
impaired
cognition
compared
younger
animals.
showed
increased
memory.
negligible
influence
most
measures.
Conclusion:
Effects
AD-like
behavioral
symptoms
subtle.
Further
investigation
different
forms
warranted.
Frontiers in Neuroscience,
Journal Year:
2020,
Volume and Issue:
14
Published: Oct. 6, 2020
The
locus
coeruleus
(LC)
has
long
been
underappreciated
for
its
role
in
the
pathophysiology
of
Alzheimer's
disease
(AD),
Parkinson's
(PD),
and
other
neurodegenerative
disorders.
While
AD
PD
are
distinct
clinical
presentation,
both
characterized
by
prodromal
protein
aggregation
LC,
late-stage
degeneration
comorbid
conditions
indicative
LC
dysfunction.
Many
these
early
studies
were
limited
to
post-mortem
histological
techniques
due
LC's
small
size
location
deep
brainstem.
Thus,
there
is
a
growing
interest
utilizing
vivo
imaging
as
predictor
preclinical
processes
biomarker
progression.
Simultaneously,
neuroimaging
animal
models
holds
promise
identifying
alterations
circuits,
but
thus
far
underutilized.
still
infancy,
handful
have
reported
effects
single
gene
mutations
pathology
on
function
using
various
techniques.
Furthermore,
combining
optogenetics
or
chemogenetics
allows
interrogation
network
connectivity
response
changes
activity.
purpose
this
article
twofold:
(1)
review
what
magnetic
resonance
(MRI)
positron
emission
tomography
(PET)
revealed
about
dysfunction
potential
humans,
(2)
explore
how
can
be
used
test
hypotheses
derived
from
data
establish
mechanistic
framework
inform
LC-focused
therapeutic
interventions
alleviate
symptoms
impede
