Proceedings of the National Academy of Sciences,
Год журнала:
2017,
Номер
114(23)
Опубликована: Май 22, 2017
Significance
Early
life
stress
(ELS)
is
an
important
risk
factor
for
schizophrenia.
Our
study
shows
that
ELS
in
mice
increases
the
levels
of
histone-deacetylase
(HDAC)
1
brain
and
blood.
Although
altered
Hdac1
expression
response
to
widespread,
increased
prefrontal
cortex
are
responsible
development
schizophrenia-like
phenotypes.
In
turn,
administration
HDAC
inhibitor
ameliorates
ELS-induced
We
also
show
brains
patients
with
schizophrenia
blood
from
who
suffered
ELS,
suggesting
analysis
could
be
used
patient
stratification
individualized
therapy.
Cell Reports,
Год журнала:
2018,
Номер
22(8), С. 2216 - 2225
Опубликована: Фев. 1, 2018
To
understand
the
cellular
basis
of
behavior,
it
is
necessary
to
know
cell
types
that
exist
in
nervous
system
and
their
contributions
function.
Spinal
networks
are
essential
for
sensory
processing
motor
behavior
provide
a
powerful
identifying
correlates
behavior.
Here,
we
used
massively
parallel
single
nucleus
RNA
sequencing
(snRNA-seq)
create
an
atlas
adult
mouse
lumbar
spinal
cord.
We
identified
molecularly
characterized
43
neuronal
populations.
Next,
leveraged
snRNA-seq
approach
unbiased
identification
populations
were
active
following
using
transcriptional
signature
activity.
This
can
be
future
link
gene
expression
data
with
dynamic
biological
responses
injury,
disease.
npj Science of Learning,
Год журнала:
2019,
Номер
4(1)
Опубликована: Июль 2, 2019
Abstract
It
has
been
70
years
since
Donald
Hebb
published
his
formalized
theory
of
synaptic
adaptation
during
learning.
Hebb’s
seminal
work
foreshadowed
some
the
great
neuroscientific
discoveries
following
decades,
including
discovery
long-term
potentiation
and
other
lasting
forms
plasticity,
more
recently
residence
memories
in
synaptically
connected
neuronal
assemblies.
Our
understanding
processes
underlying
learning
memory
dominated
by
view
that
synapses
are
principal
site
information
storage
brain.
This
received
substantial
support
from
research
several
model
systems,
with
vast
majority
studies
on
topic
corroborating
a
role
for
storage.
Yet,
despite
neuroscience
community’s
best
efforts,
we
still
without
conclusive
proof
reside
at
synapses.
Furthermore,
an
increasing
number
non-synaptic
mechanisms
have
emerged
also
capable
acting
as
substrates.
In
this
review,
address
key
findings
plasticity
literature
make
these
phenomena
such
attractive
mechanisms.
We
then
turn
our
attention
to
evidence
questions
reliance
exclusively
changes
synapse
attempt
integrate
opposing
views.
Nature Communications,
Год журнала:
2018,
Номер
9(1)
Опубликована: Окт. 8, 2018
The
turnover
of
brain
proteins
is
critical
for
organism
survival,
and
its
perturbations
are
linked
to
pathology.
Nevertheless,
protein
lifetimes
have
been
difficult
obtain
in
vivo.
They
readily
measured
vitro
by
feeding
cells
with
isotopically
labeled
amino
acids,
followed
mass
spectrometry
analyses.
In
vivo
generated
from
at
least
two
sources:
acids
the
diet,
non-labeled
degradation
pre-existing
proteins.
This
renders
measurements
difficult.
Here
we
solved
this
problem
rigorously
a
workflow
that
combines
mouse
isotopic
labeling,
spectrometry,
mathematical
modeling.
We
also
established
several
independent
approaches
test
validate
results.
enabled
us
measure
accurate
~3500
high
precision
our
data
provided
large
set
biologically
significant
observations,
including
pathway-,
organelle-,
organ-,
or
cell-specific
effects,
along
comprehensive
catalog
extremely
long-lived
(ELLPs).
Advanced Functional Materials,
Год журнала:
2018,
Номер
29(7)
Опубликована: Дек. 27, 2018
Abstract
The
myelin
sheath
enables
dramatic
speed
enhancement
for
signal
propagation
in
nerves.
In
this
work,
myelinated
nerve
structure
is
experimentally
and
theoretically
studied
using
synchrotron‐radiation‐based
Fourier‐transform
infrared
microspectroscopy.
It
found
that,
with
a
certain
mid‐infrared
to
terahertz
spectral
range,
the
possesses
≈2‐fold
higher
refraction
index
compared
outer
medium
or
inner
axon,
suggesting
that
can
serve
as
an
dielectric
waveguide.
By
calculating
correlation
between
material
characteristics
of
radical
energy
distribution
nerves,
it
demonstrated
sheath,
normal
thickness
(≈2
µm)
constant
nature,
confine
field
within
enable
at
millimeter
scale
without
loss.
supplied
amplified
when
crossing
nodes
Ranvier
via
periodic
relay.
These
findings
provide
first
model
explaining
mechanism
neurotransmission
through
which
may
promote
development
biological‐tissue
label‐free
detection,
biomaterial‐based
sensors,
neural
information,
noninvasive
brain–machine
interfaces.
Nutrients,
Год журнала:
2017,
Номер
9(8), С. 815 - 815
Опубликована: Июль 28, 2017
Choline
is
an
essential
nutrient
for
humans.
It
a
precursor
of
membrane
phospholipids
(e.g.,
phosphatidylcholine
(PC)),
the
neurotransmitter
acetylcholine,
and
via
betaine,
methyl
group
donor
S-adenosylmethionine.
High
choline
intake
during
gestation
early
postnatal
development
in
rat
mouse
models
improves
cognitive
function
adulthood,
prevents
age-related
memory
decline,
protects
brain
from
neuropathological
changes
associated
with
Alzheimer’s
disease
(AD),
neurological
damage
epilepsy,
fetal
alcohol
syndrome,
inherited
conditions
such
as
Down
Rett
syndromes.
These
effects
are
correlated
modifications
histone
DNA
methylation
brain,
alterations
expression
genes
that
encode
proteins
important
learning
processing,
suggesting
possible
epigenomic
mechanism
action.
Dietary
adult
may
also
influence
effect
on
PC
containing
eicosapentaenoic
docosahexaenoic
acids;
polyunsaturated
species
whose
levels
reduced
brains
AD
patients,
higher
performance,
resistance
to
decline.
Nature Communications,
Год журнала:
2017,
Номер
8(1)
Опубликована: Окт. 18, 2017
Chemical
modifications
on
DNA
molecules,
such
as
5-methylcytosine
and
5-hydroxymethylcytosine,
play
important
roles
in
the
mammalian
brain.
A
novel
adenine
modification,
N(6)-methyladenine
(6mA),
has
recently
been
found
cells.
However,
presence
function(s)
of
6mA
brain
remain
unclear.
Here
we
demonstrate
dynamics
mouse
response
to
environmental
stress.
We
find
that
overall
levels
are
significantly
elevated
upon
Genome-wide
transcriptome
profiling
reveal
an
inverse
association
between
dynamic
changes
a
set
upregulated
neuronal
genes
or
downregulated
LINE
transposon
expression.
Genes
bearing
stress-induced
overlap
with
loci
associated
neuropsychiatric
disorders.
These
results
suggest
epigenetic
role
for
well
its
potential
involvement
N6-methyladenine
is
covalent
modification
genome.
Here,
Yao
colleagues
show
level
following
stress,
subsequent
differential
gene
expression
correlated
Epigenetics & Chromatin,
Год журнала:
2019,
Номер
12(1)
Опубликована: Янв. 7, 2019
Epigenetic
modifications
such
as
histone
methylation
permit
change
in
chromatin
structure
without
accompanying
the
underlying
genomic
sequence.
A
number
of
studies
animal
models
have
shown
that
dysregulation
various
components
epigenetic
machinery
causes
cognitive
deficits
at
behavioral
level,
suggesting
proper
control
is
necessary
for
fundamental
processes
learning
and
memory.
Histone
H3
lysine
K4
(H3K4)
comprises
one
component
control,
global
levels
this
mark
are
increased
hippocampus
during
memory
formation.
Modifiers
H3K4
needed
formation,
through
studies,
many
same
modifiers
mutated
human
diseases.
Indeed,
all
known
methyltransferases
four
six
demethylases
been
associated
with
impaired
cognition
a
neurologic
or
psychiatric
disorder.
Cognitive
impairment
patients
often
manifests
intellectual
disability,
consistent
role
As
modification
quintessentially,
but
not
exclusively,
transcriptional
activity,
provides
unique
insights
into
regulatory
complexity
writing,
reading,
erasing
marks
within
an
activated
neuron.
The
following
review
will
discuss
connect
it
to
events
required
developed
nervous
system.
This
include
initial
discussion
most
recent
advances
developing
methodology
analyze
methylation,
namely
mass
spectrometry
deep
sequencing,
well
how
these
methods
can
be
applied
more
deeply
understand
biology
brain.
We
then
introduce
core
enzymatic
mediating
addition
removal
resulting
signatures
throughout
neuronal
genome.
next
foray
brain,
discussing
changes
formation
retrieval,
correlates
methyltransferase
deficiency
region.
Finally,
we
diseases
connected
each
modulator
summarize
drugs
target
them.
Cell Reports,
Год журнала:
2019,
Номер
26(5), С. 1174 - 1188.e5
Опубликована: Янв. 1, 2019
Neuronal
activity-inducible
gene
transcription
correlates
with
rapid
and
transient
increases
in
histone
acetylation
at
promoters
enhancers
of
activity-regulated
genes.
Exactly
how
modulates
these
genes
has
remained
unknown.
We
used
single-cell
situ
transcriptional
analysis
to
show
that
Fos
Npas4
are
transcribed
stochastic
bursts
mouse
neurons
membrane
depolarization
mRNA
expression
by
increasing
burst
frequency.
then
expressed
dCas9-p300
or
dCas9-HDAC8
fusion
proteins
mimic
block
activity-induced
locally
enhancers.
Adding
increased
prolonging
duration
resulted
higher
protein
levels
an
elevation
resting
potential.
Inhibiting
reduced
reducing
frequency
impaired
experience-dependent
induction
the
hippocampus
vivo.
Thus,
tunes
dynamics
experience-regulated
affect
selective
changes
neuronal
cellular
function.