Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home‐Cage Behavior
The Journal of Comparative Neurology,
Journal Year:
2024,
Volume and Issue:
532(7)
Published: July 1, 2024
ABSTRACT
Lafora
disease
(LD)
is
a
syndrome
of
progressive
myoclonic
epilepsy
and
cumulative
neurocognitive
deterioration
caused
by
recessively
inherited
genetic
lesions
EPM2A
(laforin)
or
NHLRC1
(malin).
Neuropsychiatric
symptomatology
in
LD
thought
to
be
directly
downstream
neuronal
astrocytic
polyglucosan
aggregates,
termed
bodies
(LBs),
which
faithfully
accumulate
an
age‐dependent
manner
all
mouse
models
LD.
In
this
study,
we
applied
home‐cage
monitoring
examine
the
extent
neurobehavioral
model
malin‐deficient
as
means
identify
robust
preclinical
endpoints
that
may
guide
selection
novel
treatments.
At
6
weeks,
∼6–7
months,
∼12
months
age,
mice
(“KO”)
wild‐type
(WT)
littermates
underwent
standardized
behavioral
assessment
designed
non‐obtrusively
appraise
features
rest/arousal,
consumptive
behaviors,
risk
aversion,
voluntary
wheel‐running.
timepoints,
over
range
metrics
report
transparently,
WT
KO
were
essentially
indistinguishable.
contrast,
within
compared
across
same
identified
age‐related
nocturnal
hypoactivity,
diminished
sucrose
preference,
reduced
Neuropathological
examinations
subsets
revealed
expected
LB
accumulation,
gliosis,
microglial
activation
cortical
subcortical
brain
regions.
12
despite
burden
neocortical
LBs,
did
not
spontaneous
seizures
during
electroencephalographic
(EEG)
survey,
exhibited
similar
spectral
EEG
features.
However,
vitro
assay
function,
paroxysmal
bursts
network
activity
(UP
states)
slices
more
prolonged
at
3
but
months.
displayed
distinct
response
pentylenetetrazole,
with
greater
incidence
clonic
pronounced
postictal
suppression
movement,
feeding,
drinking
behavior.
Together,
these
results
highlight
clinicopathologic
dissociation
LD,
where
accrual
LBs
latently
modify
circuit
function
seizure
threshold
without
clinically
meaningful
changes
Our
findings
allude
delay
between
accumulation
decline
LD:
one
provide
window
for
treatment,
whose
precise
duration
difficult
ascertain
typical
lifespan
laboratory
mouse.
Language: Английский
Behavioral video coding analysis of chronic morphine administration in rats
Biomedical Reports,
Journal Year:
2024,
Volume and Issue:
21(5)
Published: Sept. 12, 2024
The
present
study
assessed
the
behavior
of
morphine-addicted
rats
using
behavioral
video
coding
technology,
to
evaluate
effective
methods
for
identifying
morphine
addiction.
Rats
were
divided
into
a
control
group
(n=15)
and
addiction
(n=15).
model
was
established
with
14-day
increasing
dose
scheme,
confirmed
conditional
place
preference
(CPP)
experiment.
After
successful
modeling,
rats'
recorded
12
h,
then
coded
analyzed
Observer
XT
analysis
software.
Compared
group,
showed
increased
heat
pain
tolerance
time
(P=0.039)
spent
more
in
white
box
during
CPP
experiment
(P<0.001).
Video
revealed
significant
changes
compared
controls.
In
addition
being
lighter,
decreased
water
intake,
reduced
licking
forelimbs
hind
limbs,
altered
sleeping
posture
(sleeping
curled
up)
day
(all
P<0.05).
conclusion,
chronic
administration
leads
distinctive
changes,
including
frequency,
intake
sleep
posture.
analysis,
as
safe
non-invasive
method,
may
provide
convenient
efficient
approach
studying
rats.
Language: Английский