bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Aug. 25, 2022
ABSTRACT
The
assembly
of
the
mammalian
brain
is
orchestrated
by
temporally
coordinated
waves
gene
expression.
A
key
aspect
this
developmental
program
mediated
at
post-transcriptional
level
microRNAs
(miRNAs).
Deletion
neuronal
enriched
miRNAs
induces
strong
phenotypes,
and
multiple
reports
have
found
altered
levels
in
patients
with
neurodevelopmental
disorders.
However,
cellular
molecular
mechanisms
used
to
instruct
proper
development
remain
largely
unexplored.
Here,
through
screens,
we
identified
miR-218
as
a
critical
regulator
hippocampal
mice.
MiR-218
highly
expressed
hippocampus
both
excitatory
principal
neurons
GABAergic
inhibitory
interneurons.
Transient
inhibition
early
life
results
an
adult
heightened
network
activity
predisposition
seizures.
We
RNA-seq
FACS-seq
(fluorescence-activated
cell
sorting
followed
RNA-seq)
identify
global
type-specific
changes
expression
absence
narrow
down
which
processes
would
lead
long-term
instability.
find
that
disruption
depolarizing
signaling,
structural
defects
dendritic
spines,
intrinsic
membrane
excitability.
Finally,
conditional
knockout
interneurons,
but
not
pyramidal
sufficient
recapitulate
effects
on
stability.
Taken
together,
data
suggest
orchestrates
produce
stable
adult,
primarily
regulating
interneuron
function
postnatal
life.
Journal of Personalized Medicine,
Journal Year:
2022,
Volume and Issue:
12(5), P. 770 - 770
Published: May 10, 2022
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
and
Amyotrophic
Lateral
Sclerosis
(ALS)
are
representative
neurodegenerative
diseases
(NDs)
characterized
by
degeneration
of
selective
neurons,
as
well
the
lack
effective
biomarkers
therapeutic
treatments.
In
last
decade,
microRNAs
(miRNAs)
have
gained
considerable
interest
in
diagnostics
therapy
NDs,
owing
to
their
aberrant
expression
ability
target
multiple
molecules
pathways.
Here,
we
provide
an
overview
dysregulated
miRNAs
fluids
(blood
or
cerebrospinal
fluid)
nervous
tissue
AD,
PD,
ALS
patients.
By
emphasizing
those
that
commonly
these
highlight
potential
role
therapeutical
targets
describe
use
antisense
oligonucleotides
miRNA
therapies.
Journal of Translational Medicine,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Jan. 16, 2024
Abstract
Background
Parkinson’s
disease
(PD)
is
a
neurodegenerative
disorder
characterized
by
the
loss
of
dopaminergic
(DA)
neurons
in
substantia
nigra
(SN).
Microglia-mediated
neuroinflammation
has
been
largely
considered
one
main
factors
to
PD
pathology.
MicroRNA-218-5p
(miR-218-5p)
microRNA
that
plays
role
neurodevelopment
and
function,
while
its
potential
function
remains
unclear.
Methods
We
explore
involvement
miR-218-5p
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-induced
mouse
model.
The
agomir
used
for
overexpression
was
delivered
into
(SN)
bilateral
stereotaxic
infusions.
microglial
inflammation
SN
determined
using
Western
blotting
immunofluorescence.
Motor
assessed
rotarod
test.
RNA
sequencing
(RNA-seq)
performed
pathways
regulated
miR-218-5p.
target
genes
were
predicted
TargetScan
confirmed
dual
luciferase
reporter
assays.
effects
on
related
verified
murine
microglia-like
BV2
cells.
To
stimulate
cells,
SH-SY5Y
cells
treated
with
1-methyl-4-phenylpyridinium
(MPP
+
)
conditioned
media
(CM)
collected.
Results
MiR-218-5p
expression
reduced
both
MPTP-induced
mice
MPP
-treated
significantly
alleviated
inflammation,
DA
neurons,
motor
dysfunction.
sequence
gene
set
enrichment
analysis
showed
type
I
interferon
(IFN-I)
upregulated
mice,
this
upregulation
reversed
overexpression.
A
assay
Ddx41
In
vitro,
or
knockdown
inhibited
IFN-I
response
inflammatory
cytokines
stimulated
-CM.
Conclusions
suppresses
microglia-mediated
preserves
via
/IFN-I.
Hence,
miR-218-5p-
promising
therapeutic
PD.
The
assembly
of
the
mammalian
brain
is
orchestrated
by
temporally
coordinated
waves
gene
expression.
Post-transcriptional
regulation
microRNAs
(miRNAs)
a
key
aspect
this
program.
Indeed,
deletion
neuron-enriched
miRNAs
induces
strong
developmental
phenotypes,
and
miRNA
levels
are
altered
in
patients
with
neurodevelopmental
disorders.
However,
mechanisms
used
to
instruct
development
remain
largely
unexplored.
Here,
we
identified
miR-218
as
critical
regulator
hippocampal
assembly.
MiR-218
highly
expressed
hippocampus
enriched
both
excitatory
principal
neurons
(PNs)
GABAergic
inhibitory
interneurons
(INs).
Early
life
inhibition
results
an
adult
predisposition
seizures.
Changes
expression
absence
suggest
that
network
impaired.
find
disruption
early
depolarizing
signaling,
structural
defects
dendritic
spines,
intrinsic
membrane
excitability.
Conditional
knockout
Mir218-2
INs,
but
not
PNs,
sufficient
recapitulate
long-term
instability.
Finally,
de-repressing
Kif21b
Syt13,
two
targets,
phenocopies
effects
on
synchronous
activity
induced
inhibition.
Taken
together,
data
orchestrates
formative
events
PNs
INs
produce
stable
networks.
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(4)
Published: Jan. 21, 2025
Given
the
influence
of
cognitive
abilities
on
life
outcomes,
there
is
inherent
value
in
identifying
genes
involved
controlling
learning
and
memory.
Further,
dysfunction
a
core
feature
many
neuropsychiatric
disorders.
Here,
we
use
combinatory
silico
approach
to
identify
human
gene
targets
that
will
have
an
especially
high
likelihood
individually
directly
impacting
cognition.
This
broad
unbiased
screen
led
specific
identification
ARHGEF11
,
which
encodes
PDZ-RhoGEF.
PDZ-RhoGEF
largely
RhoA-specific
activator
highly
enriched
dendritic
spines,
recent
work
identified
hyperexpression
prefrontal
cortex
bipolar
disorder
subjects,
disease
characterized
by
early
emergence
persistence
scope
dysfunction.
characterize
effects
synaptic
behavioral
phenotypes,
molecular
biochemical
mechanisms
control
PDZ-RhoGEF’s
expression,
spatial
localization,
enzymatic
activity.
Importantly,
our
direct
regulators
(miR-132
DISC1)
themselves
been
repeatedly
implicated
phenotypes
humans,
including
those
caused
several
Taken
together,
findings
indicate
key
convergence
point
among
multiple
cognition-relevant
signaling
cascades
with
potential
translational
significance.
Frontiers in Cellular Neuroscience,
Journal Year:
2023,
Volume and Issue:
17
Published: May 5, 2023
Information
processing
within
neuronal
circuits
relies
on
their
proper
development
and
a
balanced
interplay
between
principal
local
inhibitory
interneurons
those
circuits.
Gamma-aminobutyric
acid
(GABA)ergic
are
remarkably
heterogeneous
population,
comprising
subclasses
based
morphological,
electrophysiological,
molecular
features,
with
differential
connectivity
activity
patterns.
microRNA
(miRNA)-dependent
post-transcriptional
control
of
gene
expression
represents
an
important
regulatory
mechanism
for
plasticity.
miRNAs
large
group
small
non-coding
RNAs
(21-24
nucleotides)
acting
as
negative
regulators
mRNA
translation
stability.
However,
while
miRNA-dependent
regulation
in
neurons
has
been
described
heretofore
several
studies,
understanding
the
role
is
only
beginning
to
emerge.
Recent
research
demonstrated
that
differentially
expressed
interneuron
subclasses,
vitally
migration,
maturation,
survival
during
embryonic
crucial
cognitive
function
memory
formation.
In
this
review,
we
discuss
recent
progress
function.
We
aim
shed
light
onto
mechanisms
by
which
GABAergic
contribute
sculpting
circuits,
how
dysregulation
may
underlie
emergence
numerous
neurodevelopmental
neuropsychiatric
disorders.