Transcriptional and functional profiles of muscarinic receptor-expressing neurons in primate lateral prefrontal and anterior cingulate cortices
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 24, 2025
Acetylcholine
modulates
anterior
cingulate
(ACC)
and
lateral
prefrontal
(LPFC)
cortices
for
cognitive-motivational
integration,
via
specific
m1-m4
muscarinic
receptors
(mAChR)
encoded
by
CHRM1-4
genes.
Single-nucleus
RNA
sequencing
mRNA-protein
histology
in
macaques
revealed
CHRM3
to
be
the
most
enriched
mAChR
gene
neurons,
while
m1
predominates
at
protein
level,
likely
due
nuclear
retention
of
cytoplasmic
trafficking
CHRM1.
CHRM1
showed
strong
co-expression
functional
overlap,
were
transcriptomically-distinct
from
CHRM2,
which
was
uniquely
deep
layer
excitatory
PVALB
+
inhibitory
neurons.
Although
CHRM
cell
distributions
similar
between
areas,
CHRM1-3
neurons
ACC
exhibited
upregulation
synaptic
plasticity
genes
relative
LPFC.
Functional
vitro
experiments
confirm
a
more
robust
cholinergic-mediated
decrease
excitatory:inhibitory
ratio
than
LPFC
accompanied
compensatory
changes
spine
morphology.
These
findings
highlight
region-specific
acetylcholine
signaling
essential
flexible
processing,
learning
memory.
Язык: Английский
Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives
Genes & Diseases,
Год журнала:
2023,
Номер
11(6), С. 101130 - 101130
Опубликована: Сен. 26, 2023
The
recent
advances
in
high
throughput
sequencing
technology
have
drastically
changed
the
practice
of
medical
diagnosis,
allowing
for
rapid
identification
hundreds
genes
causing
human
diseases.
This
unprecedented
progress
has
made
clear
that
most
forms
intellectual
disability
affect
more
than
3%
individuals
worldwide
are
monogenic
Strikingly,
a
substantial
fraction
mendelian
is
associated
with
related
to
ubiquitin-proteasome
system,
highly
conserved
pathway
up
approximately
1200
involved
regulation
protein
homeostasis.
Within
this
group
currently
emerging
new
class
neurodevelopmental
disorders
specifically
caused
by
proteasome
pathogenic
variants
which
we
propose
designate
"neurodevelopmental
proteasomopathies".
Besides
cognitive
impairment,
these
diseases
typically
series
syndromic
clinical
manifestations,
among
facial
dysmorphism,
motor
delay,
and
failure
thrive
prominent
ones.
While
efforts
been
uncover
effects
exerted
on
cell
tissue
landscapes,
molecular
pathogenesis
proteasomopathies
remains
ill-defined.
In
review,
discuss
cellular
changes
induced
genomic
alterations
explore
their
relevance
as
biomarkers
management,
potential
treatment
rare
disease
entities.
Язык: Английский
Synaptic cell adhesion molecules contribute to the pathogenesis and progression of fragile X syndrome
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Июль 3, 2024
Fragile
X
syndrome
(FXS)
is
the
most
common
form
of
inherited
intellectual
disability
and
a
monogenic
cause
autism
spectrum
disorders.
Deficiencies
in
fragile
messenger
ribonucleoprotein,
encoded
by
FMR1
gene,
lead
to
various
anatomical
pathophysiological
abnormalities
behavioral
deficits,
such
as
spine
dysmorphogenesis
learning
memory
impairments.
Synaptic
cell
adhesion
molecules
(CAMs)
play
crucial
roles
synapse
formation
neural
signal
transmission
promoting
new
synaptic
contacts,
accurately
organizing
presynaptic
postsynaptic
protein
complexes,
ensuring
accuracy
transmission.
Recent
studies
have
implicated
CAMs
immunoglobulin
superfamily,
N-cadherin,
leucine-rich
repeat
proteins,
neuroligin-1
pathogenesis
FXS
found
that
they
contribute
defects
dendritic
spines
plasticity
animal
models.
This
review
systematically
summarizes
biological
associations
between
nine
representative
FMRP,
well
functional
consequences
interaction,
provide
insights
into
mechanisms
abnormal
development
FXS.
Язык: Английский
PKA Activity-Driven Modulation of Bidirectional Long-Distance transport of Lysosomal vesicles During Synapse Maintenance
Kerriann K. Badal,
Yibo Zhao,
Bindu Raveendra
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 30, 2024
Abstract
The
bidirectional
long-distance
transport
of
organelles
is
crucial
for
cell
body-synapse
communication.
However,
the
mechanisms
by
which
this
modulated
synapse
formation,
maintenance,
and
plasticity
are
not
fully
understood.
Here,
we
demonstrate
through
quantitative
analyses
that
maintaining
sensory
neuron-motor
neuron
synapses
in
Aplysia
gill-siphon
withdrawal
reflex
linked
to
a
sustained
reduction
retrograde
lysosomal
vesicles
neurons.
Interestingly,
while
mitochondrial
anterograde
direction
increases
within
12
hours
vesicle
appears
three
days
after
formation.
Moreover,
find
formation
new
during
learning
induced
neuromodulatory
neurotransmitter
serotonin
further
reduces
24
hours,
whereas
one
hour
exposure.
Pharmacological
inhibition
several
signaling
pathways
pinpoints
PKA
as
key
regulator
maintenance.
These
results
leads
organelle-specific
specific
enduring
changes
transport,
offering
insights
into
underlying
maintenance
plasticity.
Язык: Английский