National Science Review,
Journal Year:
2019,
Volume and Issue:
6(1), P. 87 - 100
Published: Jan. 1, 2019
Circadian
disruption
is
a
risk
factor
for
metabolic,
psychiatric
and
age-related
disorders,
non-human
primate
models
could
help
to
develop
therapeutic
treatments.
Here,
we
report
the
generation
of
BMAL1
knockout
cynomolgus
monkeys
circadian-related
disorders
by
CRISPR/Cas9
editing
monkey
embryos.
These
showed
higher
nocturnal
locomotion
reduced
sleep,
which
was
further
exacerbated
constant
light
regimen.
Physiological
circadian
reflected
markedly
dampened
arrhythmic
blood
hormonal
levels.
Furthermore,
BMAL1-deficient
exhibited
anxiety
depression,
consistent
with
their
stably
elevated
cortisol,
defective
sensory
processing
in
auditory
oddball
tests
found
schizophrenia
patients.
Ablation
up-regulated
transcriptional
programs
toward
inflammatory
stress
responses,
transcription
networks
associated
human
sleep
deprivation,
major
depressive
aging.
Thus,
are
potentially
useful
studying
physiological
consequences
disturbance,
developing
therapies
disorders.
Genome Medicine,
Journal Year:
2019,
Volume and Issue:
11(1)
Published: Dec. 1, 2019
Abstract
Circadian
clocks
are
endogenous
oscillators
that
control
24-h
physiological
and
behavioral
processes.
The
central
circadian
clock
exerts
over
myriad
aspects
of
mammalian
physiology,
including
the
regulation
sleep,
metabolism,
immune
system.
Here,
we
review
advances
in
understanding
genetic
sleep
through
system,
as
well
impact
dysregulated
gene
expression
on
metabolic
function.
We
also
recent
studies
have
begun
to
unravel
clock’s
role
controlling
cardiovascular
nervous
systems,
gut
microbiota,
cancer,
aging.
Such
these
systems
relies,
part,
transcriptional
regulation,
with
evidence
for
genome-wide
chromosome
organization.
These
novel
insights
into
genomic
human
physiology
provide
opportunities
discovery
improved
treatment
strategies
new
biological
underpinnings
disease.
Journal of Clinical Investigation,
Journal Year:
2021,
Volume and Issue:
131(19)
Published: Sept. 30, 2021
Circadian
disruption
is
pervasive
and
can
occur
at
multiple
organizational
levels,
contributing
to
poor
health
outcomes
individual
population
levels.
Evidence
points
a
bidirectional
relationship,
in
that
circadian
increases
disease
severity
many
diseases
disrupt
rhythms.
Importantly,
increase
the
risk
for
expression
development
of
neurologic,
psychiatric,
cardiometabolic,
immune
disorders.
Thus,
harnessing
rich
findings
from
preclinical
translational
research
biology
enhance
via
circadian-based
approaches
represents
unique
opportunity
personalized/precision
medicine
overall
societal
well-being.
In
this
Review,
we
discuss
implications
human
using
bench-to-bedside
approach.
science
applied
clinical
population-based
Given
broad
regulation
health,
Review
focuses
its
discussion
on
selected
examples
metabolic,
cardiovascular,
allergic,
immunologic
disorders
highlight
interrelatedness
between
potential
interventions,
such
as
bright
light
therapy
exogenous
melatonin,
well
chronotherapy
improve
and/or
modify
outcomes.
Proceedings of the National Academy of Sciences,
Journal Year:
2019,
Volume and Issue:
116(11), P. 5102 - 5107
Published: Feb. 21, 2019
Circadian
dysfunction
is
a
common
attribute
of
many
neurodegenerative
diseases,
most
which
are
associated
with
neuroinflammation.
rhythm
has
been
inflammation
in
the
periphery,
but
role
core
clock
neuroinflammation
remains
poorly
understood.
Here
we
demonstrate
that
Rev-erbα,
nuclear
receptor
and
circadian
component,
mediator
microglial
activation
We
observed
time-of-day
oscillation
immunoreactivity
hippocampus,
was
disrupted
Rev-erbα
−/−
mice.
deletion
caused
spontaneous
hippocampus
increased
expression
proinflammatory
transcripts,
as
well
secondary
astrogliosis.
Transcriptomic
analysis
from
mice
revealed
predominant
inflammatory
phenotype
suggested
dysregulated
NF-κB
signaling.
Primary
microglia
exhibited
phenotypes
basal
activation.
Chromatin
immunoprecipitation
physically
interacts
promoter
regions
several
NF-κB–related
genes
primary
microglia.
Loss
astrocytes
had
no
effect
on
did
potentiate
response
to
lipopolysaccharide
(LPS).
In
vivo,
enhanced
hippocampal
neuroinflammatory
responses
peripheral
LPS
injection,
while
pharmacologic
Rev-erbs
small
molecule
agonist
SR9009
suppressed
LPS-induced
influenced
neuronal
health,
conditioned
media
Rev-erbα–deficient
glial
cultures
exacerbated
oxidative
damage
cultured
neurons.
also
significantly
altered
cortical
resting-state
functional
connectivity,
similar
models.
Our
results
reveal
pharmacologically
accessible
link
between
