bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 23, 2024
Abstract
Methylglyoxal
(MG)
is
an
endogenously
produced
non-enzymatic
side
product
of
glycolysis
that
acts
as
a
partial
agonist
at
GABA
A
receptors.
MG
metabolized
by
the
enzyme
glyoxalase-1
(GLO1).
Inhibition
GLO1
increases
methylglyoxal
levels,
and
has
been
shown
to
modulate
various
behaviors,
including
decreasing
seeking
cocaine-paired
cues
ethanol
consumption.
The
goal
these
studies
was
determine
if
inhibition
could
alter
cocaine-or
oxycodone-induced
locomotor
activation
and/or
conditioned
place
preference
(CPP)
cocaine
or
oxycodone.
We
used
both
pharmacological
genetic
manipulations
address
this
question.
Administration
inhibitor
s-bromobenzylglutathione
cyclopentyl
diester
(pBBG)
did
not
response
Additionally,
pBBG
had
no
significant
effect
on
for
Genetic
knockdown
Glo1
,
which
conceptually
similar
inhibition,
have
any
effects
preference,
nor
overexpression
affect
cocaine.
In
summary,
our
results
show
neither
influence
CPP
Aging Cell,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 9, 2024
Post-mortem
investigations
indicate
that
the
locus
coeruleus
(LC)
is
initial
site
of
hyperphosphorylated
pretangle
tau,
a
precursor
to
neurofibrillary
tangles
(NFTs)
found
in
Alzheimer's
disease
(AD).
The
presence
tau
and
NFTs
correlates
with
AD
progression
symptomatology.
LC
neuron
integrity
quantity
are
linked
cognitive
performance,
degeneration
strongly
associated
AD.
Despite
their
importance,
mechanisms
tau-induced
unclear.
This
study
examined
transcriptomic
mitochondrial
profiles
noradrenergic
neurons
after
transduction
pseudophosphorylated
human
tau.
Tau
hyperphosphorylation
increased
somatic
expression
L-type
calcium
channel
(LTCC),
impaired
health,
led
deficits
spatial
olfactory
learning.
Sex-dependent
alterations
gene
were
observed
rats
transduced
Chronic
LTCC
blockade
prevented
behavioral
altered
mRNA
expression,
suggesting
potential
link
between
hyperactivity
dysfunction.
Our
research
provides
insights
into
consequences
pathology
originating
structure
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 2, 2024
Abstract
Opioid
use
disorder
(OUD)
is
a
neuropsychological
disease
that
has
devastating
impact
on
public
health.
Substantial
individual
differences
in
vulnerability
exist,
the
neurobiological
substrates
of
which
remain
unclear.
To
address
this
question,
we
investigated
genome-wide
gene
transcription
(RNA-seq)
and
chromatin
accessibility
(ATAC-seq)
medial
prefrontal
cortex
(mPFC)
male
female
rats
exhibiting
differential
behavioral
paradigms
modeling
different
phases
OUD:
Withdrawal-Induced
Anhedonia
(WIA),
Demand,
Reinstatement.
Ingenuity
Pathway
Analysis
(IPA)
RNA-seq
revealed
greater
changes
canonical
pathways
Resilient
(vs.
Saline)
comparison
to
Vulnerable
across
3
paradigms,
suggesting
brain
adaptations
might
contribute
resilience
OUD
its
trajectory.
Analyses
networks
upstream
regulators
implicated
processes
involved
oligodendrocyte
maturation
myelination
WIA,
neuroinflammation
metabolism
Motif
analysis
ATAC-seq
showed
small
set
factor
(TF)
binding
sites
as
function
either
opioid
exposure
(i.e.,
morphine
versus
saline)
generally
or
specifically.
Some
these
were
shared
others
unique
each.
In
conclusion,
have
identified
biological
pathways,
TFs,
their
motifs
vary
with
paradigm
vulnerability.
These
findings
point
involvement
distinct
transcriptional
epigenetic
mechanisms
response
exposure,
OUD,
stages
disorder.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 8, 2024
Substance
use
disorder
(SUD)
is
a
heterogeneous
disorder,
where
severity,
symptoms,
and
patterns
of
substance
vary
across
individuals.
Yet,
when
rats
are
allowed
to
self-administer
drugs
such
as
cocaine
under
short-access
conditions,
their
behavior
tends
be
well-regulated
homogeneous
in
nature;
though
individual
differences
can
emerge
provided
long-
or
intermittent-access
cocaine.
In
contrast
cocaine,
significant
3,4-methylenedioxypyrovalerone
(MDPV),
even
wherein
~30%
rapidly
transition
high
levels
drug-taking.
This
study
assessed
the
SUD-like
phenotypes
male
female
Sprague
Dawley
self-administering
MDPV
(0.032
mg/kg/infusion)
(0.32
by
comparing
level
drug
intake,
responding
during
periods
signaled
unavailability,
sensitivity
footshock
punishment
test
hypotheses
that:
(1)
that
will
exhibit
more
robust
phenotype
than
self-administered
cocaine;
(2)
have
severe
rats;
(3)
compared
short-access,
self-administration
result
phenotype.
After
exhibited
Though
altered
drug-taking
patterns,
manipulating
access
conditions
did
not
systematically
alter
Evidence
from
behavioral
quantitative
autoradiography
studies
suggest
these
unlikely
due
changes
expression
dopamine
transporter,
D
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 23, 2024
Abstract
Methylglyoxal
(MG)
is
an
endogenously
produced
non-enzymatic
side
product
of
glycolysis
that
acts
as
a
partial
agonist
at
GABA
A
receptors.
MG
metabolized
by
the
enzyme
glyoxalase-1
(GLO1).
Inhibition
GLO1
increases
methylglyoxal
levels,
and
has
been
shown
to
modulate
various
behaviors,
including
decreasing
seeking
cocaine-paired
cues
ethanol
consumption.
The
goal
these
studies
was
determine
if
inhibition
could
alter
cocaine-or
oxycodone-induced
locomotor
activation
and/or
conditioned
place
preference
(CPP)
cocaine
or
oxycodone.
We
used
both
pharmacological
genetic
manipulations
address
this
question.
Administration
inhibitor
s-bromobenzylglutathione
cyclopentyl
diester
(pBBG)
did
not
response
Additionally,
pBBG
had
no
significant
effect
on
for
Genetic
knockdown
Glo1
,
which
conceptually
similar
inhibition,
have
any
effects
preference,
nor
overexpression
affect
cocaine.
In
summary,
our
results
show
neither
influence
CPP
