The Absence of Gastrointestinal Redox Dyshomeostasis in the Brain-First Rat Model of Parkinson’s Disease Induced by Bilateral Intrastriatal 6-Hydroxydopamine
Molecular Neurobiology,
Год журнала:
2024,
Номер
61(8), С. 5481 - 5493
Опубликована: Янв. 10, 2024
The
gut-brain
axis
plays
an
important
role
in
Parkinson's
disease
(PD)
by
acting
as
a
route
for
vagal
propagation
of
aggregated
α-synuclein
the
gut-first
endophenotype
and
mediator
gastrointestinal
dyshomeostasis
via
nigro-vagal
pathway
brain-first
disease.
One
mechanism
which
may
promote
PD
is
regulating
redox
homeostasis
overwhelming
evidence
suggests
that
oxidative
stress
key
etiopathogenesis
progression
tract
maintains
organism
critical
barrier
to
environmental
microbiological
electrophilic
challenges.
present
aim
was
utilize
bilateral
intrastriatal
6-hydroxydopamine
(6-OHDA)
model
study
effects
isolated
central
pathology
on
tract.
Three-month-old
male
Wistar
rats
were
either
not
treated
(intact
controls;
CTR)
or
bilaterally
intrastriatally
with
vehicle
(CIS)
6-OHDA
(6-OHDA).
Motor
deficits
assessed
rotarod
performance
test,
duodenum,
ileum,
colon
dissected
biochemical
analyses
12
weeks
after
treatment.
Lipid
peroxidation,
total
antioxidant
capacity,
low-molecular-weight
thiols,
protein
sulfhydryls,
activity
Mn/Fe
superoxide
dismutases,
azide-insensitive
catalase/peroxidase
measured.
Both
univariate
multivariate
models
analyzing
biomarkers
indicate
significant
disturbances
balance
are
present.
findings
demonstrate
motor
impairment
observed
can
occur
without
concurrent
imbalances
system.
Язык: Английский
Insights into Gastrointestinal Redox Dysregulation in a Rat Model of Alzheimer’s Disease and the Assessment of the Protective Potential of D-Galactose
ACS Omega,
Год журнала:
2024,
Номер
9(10), С. 11288 - 11304
Опубликована: Фев. 27, 2024
Recent
evidence
suggests
that
the
gut
plays
a
vital
role
in
development
and
progression
of
Alzheimer's
disease
(AD)
by
triggering
systemic
inflammation
oxidative
stress.
The
well-established
rat
model
AD,
induced
intracerebroventricular
administration
streptozotocin
(STZ-icv),
provides
valuable
insights
into
GI
implications
neurodegeneration.
Notably,
this
leads
to
pathophysiological
changes
gut,
including
redox
dyshomeostasis,
resulting
from
central
neuropathology.
Our
study
aimed
investigate
mechanisms
underlying
dyshomeostasis
assess
effects
D-galactose,
which
is
known
benefit
homeostasis
alleviate
cognitive
deficits
model.
Duodenal
rings
isolated
STZ-icv
animals
control
groups
were
subjected
prooxidative
environment
using
2,2′-azobis(2-amidinopropane)
dihydrochloride
(AAPH)
or
H2O2
with
without
D-galactose
oxygenated
Krebs
buffer
ex
vivo.
Redox
was
analyzed
through
protein
microarrays
functional
biochemical
assays
alongside
cell
survival
assessment.
Structural
equation
modeling
univariate
multivariate
models
employed
evaluate
differential
response
samples
controlled
challenge.
showed
suppressed
expression
catalase
glutathione
peroxidase
4
(GPX4)
increased
baseline
activity
enzymes
involved
superoxide
homeostasis.
altered
status
associated
an
inability
respond
challenges
D-galactose.
Conversely,
presence
antioxidant
capacity,
enhanced
activity,
upregulated
dismutases
samples.
STZ-icv-induced
dysfunction
characterized
diminished
ability
regulatory
system
maintain
long-term
protection
transcription
genes
as
well
compromised
activation
responsible
for
immediate
defense.
can
exert
beneficial
on
under
physiological
conditions.
Язык: Английский
Association of Cognitive Deficit with Glutamate and Insulin Signaling in a Rat Model of Parkinson’s Disease
Biomedicines,
Год журнала:
2023,
Номер
11(3), С. 683 - 683
Опубликована: Фев. 23, 2023
Cognitive
deficit
is
a
frequent
non-motor
symptom
in
Parkinson's
disease
(PD)
with
an
unclear
pathogenesis.
Recent
research
indicates
possible
involvement
of
insulin
resistance
and
glutamate
excitotoxicity
PD
development.
We
investigated
cognitive
performance
the
brain
signaling
rat
model
induced
by
bilateral
intrastriatal
injection
6-hydroxydopamine
(6-OHDA).
functions
were
assessed
Passive
Avoidance
(PA)
Morris
Water
Maze
(MWM)
tests.
The
expression
tyrosine
hydroxylase
(TH)
proteins
involved
(insulin
receptor
-
IR,
phosphoinositide
3
kinase
pI3K,
extracellular
signal-regulated
kinases-ERK)
(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid
receptos-AMPAR,
N-methyl-D-aspartate
NMDAR)
was
hippocampus
(HPC),
hypothalamus
(HPT)
striatum
(S)
immunofluorescence,
Western
blot
enzyme-linked
immunosorbent
assay
(ELISA).
Three
months
after
6-OHDA
treatment,
accompanied
decreased
AMPAR
activity
TH
levels
(HPC,
S),
while
remained
largely
unchanged.
Spearman's
rank
correlation
revealed
strong
positive
for
pAMPAR-PA
(S),
pNMDAR-pI3K
(HPC)
pNMDAR-IR
(all
regions).
Additionally,
found
TH-ERK
TH-pI3K,
negative
one
TH-MWM/errors
pI3K-MWM/time
(S).
These
results
suggest
association
between
(but
not
insulin)
dysfunction
model,
detected
three
treatment.
Язык: Английский
Unveiling the Journey from the Gut to the Brain: Decoding Neurodegeneration–Gut Connection in Parkinson’s Disease
ACS Chemical Neuroscience,
Год журнала:
2024,
Номер
15(13), С. 2454 - 2469
Опубликована: Июнь 19, 2024
Parkinson's
disease,
a
classical
motor
disorder
affecting
the
dopaminergic
system
of
brain,
has
been
as
disease
but
this
notion
now
viewed
differently
pathology
begins
in
gut
and
then
gradually
moves
up
to
brain
regions.
The
microorganisms
play
critical
role
maintaining
physiology
from
barrier
integrity
secretion
microbial
products
that
maintain
healthy
state.
subsequently
alters
normal
composition
microbes
causes
deleterious
effects
ultimately
trigger
strong
neuroinflammation
nonmotor
symptoms
along
with
characteristic
synucleopathy,
pathological
hallmark
disease.
Understanding
complex
pathomechanisms
distinct
established
preclinical
models
is
primary
goal
researchers
decipher
how
exactly
central
effect;
quest
led
many
answered
some
open-ended
questions
for
researchers.
We
summarize
popular
opinions
contrasting
views,
concise
footsteps
treatment
strategies
targeting
gastrointestinal
system.
Язык: Английский
Exploratory Study of Gastrointestinal Redox Biomarkers in the Presymptomatic and Symptomatic Tg2576 Mouse Model of Familial Alzheimer’s Disease: Phenotypic Correlates and Effects of Chronic Oral d-Galactose
ACS Chemical Neuroscience,
Год журнала:
2023,
Номер
14(22), С. 4013 - 4025
Опубликована: Ноя. 6, 2023
The
gut
might
play
an
important
role
in
the
etiopathogenesis
of
Alzheimer's
disease
(AD)
as
gastrointestinal
alterations
often
precede
development
neuropathological
changes
brain
and
correlate
with
progression
animal
models.
has
immense
capacity
to
generate
free
radicals
whose
AD
is
well-known;
however,
it
remains
be
clarified
whether
redox
homeostasis
associated
AD.
aim
was
(i)
examine
presymptomatic
symptomatic
Tg2576
mouse
model
AD;
(ii)
investigate
effects
oral
d-galactose
previously
shown
alleviate
cognitive
deficits
metabolic
models
reduce
oxidative
stress;
(iii)
association
between
biomarkers
behavioral
mice.
In
stage,
mice
displayed
increased
electrophilic
tone,
characterized
by
higher
lipid
peroxidation
elevated
Mn/Fe-SOD
activity.
these
are
rectified,
but
total
antioxidant
decreased.
Chronic
reduced
had
opposite
wild-type
animals.
tract
greater
spatial
memory.
Gut
involved
pathophysiology
should
further
explored
this
context.
Язык: Английский