International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(22), P. 12156 - 12156
Published: Nov. 12, 2024
In
this
study,
the
distinct
patterns
of
glial
response
and
neurodegeneration
within
CA1,
CA3,
dentate
gyrus
(DG)
regions
hippocampus
were
examined
in
5XFAD
mice
at
6
12
months
age.
The
primary
feature
transgenic
mouse
model
is
rapid
onset
amyloid
pathology.
We
employed
quantitative
assessments
via
immunohistochemistry,
incorporating
double
staining
techniques,
followed
by
observation
with
light
microscopy
subsequent
digital
analysis
microscopic
images.
identified
significantly
increased
Aβ
deposition
these
three
hippocampal
mice.
Moreover,
CA1
CA3
showed
higher
vulnerability,
signs
reactive
astrogliosis
such
as
astrocyte
density
elevated
GFAP
expression.
Additionally,
we
observed
a
significant
rise
microglia
density,
along
inflammatory
markers
(TNFα)
regions.
These
findings
highlight
non-uniform
neuronal
to
plaque
5xFAD
mice,
potentially
contributing
neurodegenerative
memory
deficit
characteristics
Alzheimer's
disease
model.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 8, 2024
Abstract
Cell
assemblies
are
believed
to
represent
the
substrate
of
memory.
Although
long-term
plasticity
likely
enables
formation
cell
assemblies,
how
other
factors,
such
as
astrocytes
and
short-term
(STP),
affect
their
properties
is
poorly
understood.
To
close
this
gap,
we
investigated
assembly
dynamics
in
a
recurrent
network
model
mimicking
hippocampal
area
CA3.
As
shown
experiment,
connections
our
obey
symmetric
spike-timing-dependent
(STDP),
which
weight
change
may
or
not
depend
on
releasable
amount
neurotransmitter.
The
former
case
involves
an
interplay
between
STDP
STP.
In
addition,
implicitly
modeled
effect
astrocyte
NMDA
receptors
by
manipulating
breadth
distribution
neurotransmitter
release
probability
Both
STP-dependent
STP-independent
enabled
spontaneous
formation.
Under
former,
however,
tend
be
smaller
more
responsive
external
stimulation,
improving
network’s
memory
capacity
enabling
flexible
restructuring.
Furthermore,
regulation
facilitates
stimulus-driven
reorganization
neural
networks
without
destroying
existing
structure,
thus
balancing
assemblies’
flexibility
robustness.
Our
findings
elucidate
computational
advantages
interaction
STP
highlight
astrocytes’
possible
regulatory
role
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Aug. 10, 2024
Astrocytes
display
context-specific
diversity
in
their
functions
and
respond
to
noxious
stimuli
between
brain
regions.
Astrocytic
mitochondria
have
emerged
as
key
players
governing
astrocytic
functional
heterogeneity,
given
ability
dynamically
adapt
morphology
regional
demands
on
ATP
generation
Ca2+
buffering
functions.
Although
there
is
reciprocal
regulation
mitochondrial
dynamics
signaling
astrocytes,
the
extent
of
this
astrocytes
from
different
regions
remains
unexplored.
Brain-wide,
experimentally
induced
DNA
(mtDNA)
loss
showed
that
mtDNA
integrity
critical
for
astrocyte
function,
however,
possible
diverse
responses
stimulus
areas
were
not
reported
these
experiments.
To
selectively
damage
a
brain-region-specific
manner,
we
developed
novel
adeno-associated
virus
(AAV)-based
tool,
Mito-PstI
expressing
restriction
enzyme
PstI,
specifically
mitochondria.
Here,
applied
two
regions,
dorsolateral
striatum
dentate
gyrus,
show
induces
vivo,
but
with
remarkable
brain-region-dependent
differences
dynamics,
fluxes,
microglial
reactivity.
Thus,
AAV-Mito-PstI
tool
explore
relationship
network
brain-region-selective
manner.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(22), P. 12156 - 12156
Published: Nov. 12, 2024
In
this
study,
the
distinct
patterns
of
glial
response
and
neurodegeneration
within
CA1,
CA3,
dentate
gyrus
(DG)
regions
hippocampus
were
examined
in
5XFAD
mice
at
6
12
months
age.
The
primary
feature
transgenic
mouse
model
is
rapid
onset
amyloid
pathology.
We
employed
quantitative
assessments
via
immunohistochemistry,
incorporating
double
staining
techniques,
followed
by
observation
with
light
microscopy
subsequent
digital
analysis
microscopic
images.
identified
significantly
increased
Aβ
deposition
these
three
hippocampal
mice.
Moreover,
CA1
CA3
showed
higher
vulnerability,
signs
reactive
astrogliosis
such
as
astrocyte
density
elevated
GFAP
expression.
Additionally,
we
observed
a
significant
rise
microglia
density,
along
inflammatory
markers
(TNFα)
regions.
These
findings
highlight
non-uniform
neuronal
to
plaque
5xFAD
mice,
potentially
contributing
neurodegenerative
memory
deficit
characteristics
Alzheimer's
disease
model.