Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 14, 2024
Background
BMAL1,
a
key
regulator
of
circadian
rhythms,
plays
multifaceted
role
in
brain
function.
However,
the
complex
interplay
between
memory,
neuroinflammation,
and
neurotransmitter
regulation
remains
poorly
understood.
To
investigate
these
interactions,
we
conducted
study
using
BMAL1-haplodeficient
mice
(BMAL1
+/−
).
Methods
We
exposed
BMAL1
to
behavioral
assessments
including
cued
fear
conditioning,
new
objection
recognition
(NOR)
test,
Y-maze
test
evaluate
haplodeficiency
impact
on
memory.
Furthermore,
biochemical
changes
were
analyzed
through
western
blotting,
ELISA
explore
further
mechanism
neuroinflammation.
Results
found
that
haploinsufficiency
led
deficits
learning
while
spatial
memory
object
remained
intact.
Further
analysis
revealed
dysregulated
levels
alterations
neurotransmitter-related
proteins
prefrontal
cortex
mice.
Pharmacological
interventions
targeting
dopamine
uptake
or
5-HT2C
receptor
demonstrated
inhibiting
could
rescue
impairments
Additionally,
observed
downregulation
inflammasome
neuroinflammation
pathways
mice,
which
is
validated
by
inflammation
mediator
lipopolysaccharide
(LPS)
administration.
Conclusion
These
findings
highlight
leads
are
linked
neurotransmitters
receptors,
particularly
receptor.
Targeting
may
offer
potential
therapeutic
strategy
for
mitigating
cognitive
associated
with
dysfunction.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 28, 2025
Summary
Critical
periods
are
developmental
windows
of
high
experience-dependent
plasticity
essential
for
the
correct
refinement
neuronal
circuitry
and
function.
While
consequences
visual
system
sensory
deprivation
during
critical
period
have
been
well-characterized,
far
less
is
known
about
effects
enhanced
experience.
Here,
we
use
prey
capture
learning
to
assess
structural
functional
mediating
in
primary
cortex
mice.
We
show
that
improves
temporal
frequency
discrimination
drives
a
profound
remodeling
through
an
increase
excitatory
connectivity
spine
turnover.
This
global
persistent
rewiring
not
observed
adult
hunters
mediated
by
TNFα-dependent
mechanisms.
Our
findings
demonstrate
experience
naturalistic
paradigm
can
drive
improve
function,
promotes
long-lasting
dynamics
could
enhance
subsequent
plasticity.
Alzheimer s & Dementia,
Год журнала:
2024,
Номер
20(7), С. 4677 - 4691
Опубликована: Июнь 3, 2024
Individuals
referred
to
as
Non-Demented
with
Alzheimer's
Neuropathology
(NDAN)
exhibit
cognitive
resilience
despite
presenting
disease
(AD)
histopathological
signs.
Investigating
the
mechanisms
behind
this
may
unveil
crucial
insights
into
AD
resistance.
Proceedings of the Japan Academy Series B,
Год журнала:
2023,
Номер
99(8), С. 254 - 305
Опубликована: Окт. 10, 2023
Recent
research
extends
our
understanding
of
brain
processes
beyond
just
action
potentials
and
chemical
transmissions
within
neural
circuits,
emphasizing
the
mechanical
forces
generated
by
excitatory
synapses
on
dendritic
spines
to
modulate
presynaptic
function.
From
in
vivo
vitro
studies,
we
outline
five
central
principles
synaptic
mechanics
function:
P1:
Stability
-
Underpinning
integral
relationship
between
structure
function
spine
synapses.
P2:
Extrinsic
dynamics
Highlighting
synapse-selective
structural
plasticity
which
plays
a
crucial
role
Hebbian
associative
learning,
distinct
from
pathway-selective
long-term
potentiation
(LTP)
depression
(LTD).
P3:
Neuromodulation
Analyzing
G-protein-coupled
receptors,
particularly
dopamine
time-sensitive
modulation
learning
frameworks
such
as
Pavlovian
classical
conditioning
Thorndike's
reinforcement
(RL).
P4:
Instability
Addressing
intrinsic
memory
management
during
continual
spotlighting
their
"spine
dysgenesis"
associated
with
mental
disorders.
P5:
Mechanics
Exploring
how
influence
both
sides
establish
traces
short-
memory,
thereby
aiding
integration
functions.
We
also
delve
into
historical
background
foresee
impending
challenges.
Journal of Neurophysiology,
Год журнала:
2024,
Номер
132(2), С. 531 - 543
Опубликована: Авг. 1, 2024
Intermittent
hypoxia
(IH)
and
high-intensity
interval
training
(HIIT)
enhance
neuroplasticity
upregulate
neurotrophic
factors
in
the
central
nervous
system
(CNS).
We
provide
evidence
that
IH
+
HIIT
also
have
capacity
to
regulate
genes
involved
RhoA/ROCK
signaling
pathway
is
known
restrict
structural
plasticity
CNS.
This
provides
a
new
mechanistic
insight
into
how
these
interventions
may
hippocampal-related
facilitate
learning,
memory,
neuroregeneration.
Pflügers Archiv - European Journal of Physiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 9, 2024
Neurons
in
central
nervous
systems
receive
multiple
synaptic
inputs
and
transform
them
into
a
largely
standardized
output
to
their
target
cells-the
action
potential.
A
simplified
model
posits
that
signals
are
integrated
by
linear
summation
passive
propagation
towards
the
axon
initial
segment,
where
threshold
for
spike
generation
is
either
crossed
or
not.
However,
lines
of
research
during
past
decades
have
shown
signal
integration
individual
neurons
much
more
complex,
with
important
functional
consequences
at
cellular,
network,
behavioral-cognitive
level.
The
interplay
between
concomitant
excitatory
inhibitory
postsynaptic
potentials
depends
strongly
on
relative
timing
localization
respective
synapses.
In
addition,
dendrites
contain
voltage-dependent
conductances,
which
allow
scaling
potentials,
non-linear
input
processing,
compartmentalization
signals.
Together,
these
features
enable
rich
variety
single-neuron
computations,
including
operations
plasticity.
Hence,
we
revise
over-simplified
messages
from
textbooks
use
computational
models
like
integrate-and-fire
some
caution.
This
concept
article
summarizes
most
mechanisms
dendritic
highlights
recent
developments
field.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 11, 2024
Abstract
Azadiradione
is
a
brain
permeable
phytochemical
present
in
the
seed
of
an
Indian
medicinal
plant,
Azadirachta
Indica,
well-known
as
Neem.
Recently,
this
small
bioactive
molecule
has
been
revealed
to
induce
expression
Ube3a,
ubiquitin
ligase
whose
loss
and
gain
function
associated
with
two
diverse
neurodevelopmental
disorders.
Here
we
report
that
in
uteroexposure
azadiradione
mice
result
severe
developmental
disabilities.
Treatment
well
tolerated
dose
into
pregnant
dam
(at
embryonic
day
12
14)
causes
substantial
decrease
body
weight
new-born
pups
at
their
early
periods
along
significant
cognitive,
motor
communication
deficits
increased
anxiety-like
behaviours.
As
animals
grow
from
adolescent
adult,
many
behavioural
are
gradually
restored
normalcy,
although,
cognitive
deficit
persists
significantly.
Biochemical
analysis
reveals
prenatally
exposed
exhibits
about
2-3
fold
increase
level
Ube3a
post
natal
25
some
its
target
proteins
linked
synaptic
plasticity
indicating
enduring
effect
drug
on
expression.
The
also
display
number
dendritic
spines
hippocampal
cortical
pyramidal
neurons.
These
results
suggest
might
be
one
key
players
azadiradione-induced
