Research Square (Research Square),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Dec. 29, 2022
Abstract
Cannabis
use
is
highly
prevalent
especially
among
people
living
with
HIV
(PLWH).
Activation
of
the
anti-inflammatory
and
neuroprotective
endocannabinoid
system
by
phytocannabinoids,
i.e.
Δ
9
-tetrahydrocannabinol
(THC),
has
been
proposed
to
reduce
symptoms.
However,
THC’s
effects
on
HIV-associated
cognitive
impairments
are
unclear.
Using
HIV-1
Tat
transgenic
mice,
current
study
investigates
acute
THC
various
behavioral
outcomes
system.
Minor
or
no
doses
(1,
3,
10
mg/kg)
were
noted
for
body
mass,
temperature,
locomotor
activity,
coordination,
but
spontaneous
nociception
was
significantly
decreased,
induction
increasing
antinociceptive
effects.
Anxiogenic
(10
demonstrated
in
Tat(−)
females
males
compared
vehicle-treated
overall
increased
anxiety-like
behavior
males.
Object
recognition
memory
diminished
injections
not
Tat(+)
females,
without
affecting
For
related
lipids,
THC,
female
sex
associated
elevated
2-AG,
AEA,
AA,
CB
1
R,
2
FAAH
and/or
MAGL
expression
CNS
regions.
Further,
higher
AEA
levels
most
structures,
prefrontal
cortex
negatively
memory.
Overall,
findings
indicate
that
exposure
exerts
differential
context
neuroHIV
dependent
sex,
potentially
due
an
altered
system,
which
may
be
relevance
view
potential
cannabis-based
treatment
options
PLWH.
Frontiers in Neuroscience,
Journal Year:
2024,
Volume and Issue:
18
Published: March 5, 2024
Background
Some
evidence
suggests
that
cannabidiol
(CBD)
has
potential
to
help
alleviate
HIV
symptoms
due
its
antioxidant
and
anti-inflammatory
properties.
Here
we
examined
acute
CBD
effects
on
various
behaviors
the
endocannabinoid
system
in
Tat
transgenic
mice.
Methods
mice
(female/male)
were
injected
with
(3,
10,
30
mg/kg)
assessed
for
antinociception,
activity,
coordination,
anxiety-like
behavior,
recognition
memory.
Brains
taken
quantify
endocannabinoids,
cannabinoid
receptors,
catabolic
enzymes.
Additionally,
metabolite
7-hydroxy-CBD
quantified
plasma
cortex.
Results
decreased
supraspinal-related
nociception
locomotion.
sex
had
little
no
any
of
behavioral
measures.
For
male
was
associated
elevated
concentration
proinflammatory
arachidonic
acid
CNS
regions,
including
cerebellum
also
showed
higher
FAAH
expression
levels
Tat(+)
males.
GPR55
striatum
females
compared
metabolism
altered
by
expression.
Conclusion
Findings
indicate
are
not
Tat,
minimal
behavior
system.
iScience,
Journal Year:
2025,
Volume and Issue:
28(3), P. 112075 - 112075
Published: Feb. 22, 2025
Despite
advancements
in
combined
antiretroviral
therapy,
human
immunodeficiency
virus
(HIV)-associated
neurocognitive
disorder
(HAND)
continue
to
affect
40%-50%
of
people
living
with
HIV.
While
neuroimaging
studies
have
revealed
HIV-1-induced
alterations
cortical
networks
and
brain
macrostructures,
it
still
remains
unclear
how
individual
neurons
the
medial
prefrontal
cortex
(mPFC)
are
affected
during
recognition
memory.
Using
vivo
calcium
imaging
an
HIV-1
transactivator
transcription
(Tat)
transgenic
mouse
model,
we
examined
mPFC
neuronal
activity
a
novel
object
memory
task.
Our
findings
show
that
HIV
Tat
expression
reduces
overall
Tat(+)
mice
without
altering
number
activated
cells.
Moreover,
distinct
subpopulations
up-
downmodulated
both
Tat(-)
depending
on
exploration.
Importantly,
familiarity-driven
increases
were
disrupted
by
expression.
These
enhance
our
understanding
HAND
may
inform
future
pharmacological
strategies
aimed
at
restoring
cognitive
function.
Cannabis and Cannabinoid Research,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 23, 2024
Background:
Evidence
suggests
that
monoacylglycerol
lipase
(MAGL)
inhibitors
can
potentially
treat
HIV
symptoms
by
increasing
the
concentration
of
2-arachidonoylglycerol
(2-AG).We
examined
a
selective
MAGL
inhibitor
ABX1431
in
context
neuroHIV.Methods:
To
assess
effects
ABX1431,
we
conducted
vitro
and
vivo
studies.In
calcium
imaging
on
frontal
cortex
neuronal
cultures
was
performed
to
evaluate
role
(10,
30,
100
nM)
transactivator
transcription
(Tat)-induced
hyperexcitability.Following
experiments,
experiments
were
using
Tat
transgenic
male
mice.Mice
treated
with
4
mg/kg
assessed
for
antinociception
tail-flick
hot
plate
assays
followed
locomotor
activity.After
behavioral
their
brains
harvested
quantify
endocannabinoids
(eCB)
related
lipids
through
mass
spectrometry,
cannabinoid
type-1
-2
receptors
(CB
1
R
CB
2
R)
quantified
western
blot.Results:
In
studies
revealed
adding
directly
significantly
increased
intracellular
concentration,
which
completely
reversed
at
all
concentrations.Preincubating
antagonists
showed
exhibited
its
partially
R.In
demonstrated
acute
overall
total
distance
traveled
speed
mice
regardless
genotype.Mass
spectrometry
blot
analyses
differential
eCB
system
based
expression.The
2-AG
levels
upregulated
following
treatment
striatum
spinal
cord.Arachidonic
acid
(AA)
also
vehicle-treated
Tat(
+
)
mice.No
changes
noted
expression
levels;
however,
ABX1431-treated
Tat(À)
only.
Conclusion:Findings
indicate
has
potential
neuroprotective
mediated
R.
Acute
shows
antinociceptive
effects,
seems
alter
activity,
upregulating
cord.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 3, 2024
Monoacylglycerol
lipase
(MAGL)
is
a
key
enzyme
involved
in
the
metabolism
of
endogenous
signaling
ligand
2-arachidonoylglycerol,
neuroprotective
endocannabinoid
intimately
linked
to
central
nervous
system
(CNS)
disorders
associated
with
neuroinflammation.
In
quest
for
novel
MAGL
inhibitors,
focused
screening
approach
on
Roche
library
subset
provided
reversible
benzoxazinone
hit
exhibiting
high
efficiency.
The
subsequent
design
three-dimensional
Cells,
Journal Year:
2022,
Volume and Issue:
11(5), P. 857 - 857
Published: March 2, 2022
(1)
Background.
The
endocannabinoid
(eCB)
system,
which
regulates
physiological
and
cognitive
processes,
presents
a
promising
therapeutic
target
for
treating
HIV-associated
neurocognitive
disorders
(HAND).
Here
we
examine
whether
upregulating
eCB
tone
has
potential
protective
effects
against
HIV-1
Tat
(a
key
HIV
transactivator
of
transcription)
protein-induced
alterations
in
synaptic
activity.
(2)
Methods.
Whole-cell
patch-clamp
recordings
were
performed
to
assess
inhibitory
GABAergic
neurotransmission
prefrontal
cortex
slices
transgenic
male
female
mice,
the
presence
absence
fatty
acid
amide
hydrolase
(FAAH)
enzyme
inhibitor
PF3845.
Western
blot
mass
spectrometry
analyses
assessed
cannabinoid
receptor
protein
expression
as
well
endogenous
ligands,
respectively,
determine
impact
exposure
on
system.
(3)
Results.
activity
was
significantly
altered
upon
based
sex,
whereas
effectiveness
PF3845
suppress
mice
not
by
or
sex
involved
CB1R-related
mechanisms
that
depended
calcium
signaling.
Additionally,
our
data
indicated
sex-dependent
changes
AEA
related
non-eCB
lipids
induction.
(4)
Conclusion.
Results
highlight
sex-
and/or
Tat-dependent
signaling
further
increase
understanding
about
role
FAAH
inhibition
neuroHIV.
Brain Research,
Journal Year:
2023,
Volume and Issue:
1822, P. 148638 - 148638
Published: Oct. 17, 2023
Cannabis
use
is
highly
prevalent
especially
among
people
living
with
HIV
(PLWH).
Activation
of
the
anti-inflammatory
and
neuroprotective
endocannabinoid
system
by
phytocannabinoids,
i.e.
Δ
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(6), P. e0305868 - e0305868
Published: June 24, 2024
The
cannabinoid
receptor
type
1
(CB
R)
is
a
promising
therapeutic
target
for
various
neurodegenerative
diseases,
including
HIV-1-associated
neurocognitive
disorder
(HAND).
However,
the
potential
of
CB
R
by
direct
activation
limited
due
to
its
psychoactive
side
effects.
Therefore,
research
has
focused
on
indirectly
activating
utilizing
positive
allosteric
modulators
(PAMs).
Studies
have
shown
that
PAMs
(ZCZ011
and
GAT211)
are
effective
in
mouse
models
Huntington’s
disease
neuropathic
pain,
hence,
we
assess
ZCZ011
well-established
model
neuroHIV.
current
study
investigates
effect
chronic
treatment
(14
days)
behavioral
paradigms
endocannabinoid
system
HIV-1
Tat
transgenic
female
male
mice.
Chronic
(10
mg/kg)
did
not
alter
body
mass,
locomotor
activity,
or
anxiety-like
behavior
regardless
sex
genotype.
differential
effects
were
noted
hot
plate
latency,
motor
coordination,
recognition
memory
mice
only,
with
increasing
latency
improving
coordination
memory.
Only
minor
no
alterations
seen
related
lipids
except
cerebellum,
where
was
more
pronounced
Moreover,
AEA
PEA
levels
cerebellum
positively
correlated
improved
In
summary,
these
findings
indicate
antinociception,
memory,
based
expression,
making
options
HAND
without
PLoS ONE,
Journal Year:
2022,
Volume and Issue:
17(9), P. e0268590 - e0268590
Published: Sept. 9, 2022
Chronic
inflammation
and
blood–brain
barrier
dysfunction
are
key
pathological
hallmarks
of
neurological
disorders
such
as
multiple
sclerosis,
Alzheimer’s
disease
Parkinson’s
disease.
Major
drivers
these
pathologies
include
pro-inflammatory
stimuli
prostaglandins,
which
produced
in
the
central
nervous
system
by
oxidation
arachidonic
acid
a
reaction
catalyzed
cyclooxygenases
COX1
COX2.
Monoacylglycerol
lipase
hydrolyzes
endocannabinoid
signaling
lipid
2-arachidonyl
glycerol,
enhancing
local
pools
brain
leading
to
cyclooxygenase-mediated
prostaglandin
production
neuroinflammation.
inhibitors
were
recently
shown
act
effective
anti-inflammatory
modulators,
increasing
glycerol
levels
while
reducing
including
PGE
2
PGD
.
In
this
study,
we
characterized
novel,
highly
selective,
potent
reversible
monoacylglycerol
inhibitor
(MAGLi
432)
mouse
model
lipopolysaccharide-induced
permeability
both
human
cells
neurovascular
unit:
microvascular
endothelial
cells,
pericytes
astrocytes.
We
confirmed
expression
specific
unit
vitro
,
with
showing
highest
level
activity.
However,
MAGLi
432
did
not
ameliorate
vivo
or
reduce
cytokines
brain.
Our
data
confirm
provide
basis
for
further
cell-specific
analysis
context
caused
inflammatory
insults.
Viruses,
Journal Year:
2023,
Volume and Issue:
15(3), P. 590 - 590
Published: Feb. 21, 2023
Opioid
use
disorder
(OUD)
and
HIV
are
comorbid
epidemics
that
can
increase
depression.
the
viral
protein
Tat
directly
induce
neuronal
injury
within
reward
emotionality
brain
circuitry,
including
prefrontal
cortex
(PFC).
Such
damage
involves
both
excitotoxic
mechanisms
more
indirect
pathways
through
neuroinflammation,
of
which
be
worsened
by
opioid
co-exposure.
To
assess
whether
excitotoxicity
and/or
neuroinflammation
might
drive
depressive
behaviors
in
persons
infected
with
(PWH)
those
who
opioids,
male
mice
were
exposed
to
HIV-1
for
eight
weeks,
given
escalating
doses
morphine
during
last
two
assessed
depressive-like
behavior.
expression
decreased
sucrose
consumption
adaptability,
whereas
administration
increased
chow
exacerbated
Tat-induced
decreases
nesting
burrowing-activities
associated
well-being.
Across
all
treatment
groups,
behavior
correlated
proinflammatory
cytokines
PFC.
Nevertheless,
supporting
theory
innate
immune
responses
adapt
chronic
exposure,
most
unaffected
or
morphine.
Further,
PFC
levels
anti-inflammatory
cytokine
IL-10,
administration.
Tat,
but
not
morphine,
dendritic
spine
density
on
layer
V
pyramidal
neurons
anterior
cingulate.
Together,
our
findings
suggest
differentially
synaptic
losses,
fatigue