Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: March 14, 2025
Astrocytes
are
closely
linked
to
depression,
and
the
prefrontal
cortex
(PFC)
is
an
important
brain
region
involved
in
major
depressive
disorder
(MDD).
However,
underlying
mechanism
by
which
astrocytes
within
PFC
contribute
MDD
remains
unclear.
Using
single-nucleus
RNA
sequencing
analyses,
we
show
a
significant
reduction
attenuated
pleiotrophin-protein
tyrosine
phosphatase
receptor
type
Z1
(PTN-PTPRZ1)
signaling
astrocyte-to-excitatory
neuron
communication
of
male
patients.
We
find
reduced
PTN
dorsomedial
mice
with
depression
induced
chronic
restraint
social
defeat
stress.
Knockdown
astrocytic
induces
depression-related
responses,
reversed
exogenous
supplementation
or
overexpression
PTN.
The
antidepressant
effects
exerted
require
interaction
PTPRZ1
excitatory
neurons,
PTN-PTPRZ1
activates
AKT
pathway
regulate
responses.
Our
findings
indicate
PTN-PTPRZ1-AKT
may
be
potential
therapeutic
target
for
MDD.
but
mechanisms
remain
Here,
authors
that
pleiotrophin
contributes
depression-like
phenotype
mice.
Language: Английский
Pharmacological inhibition of receptor protein tyrosine phosphatase β/ζ decreases Aβ plaques and neuroinflammation in the hippocampus of APP/PS1 mice
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Dec. 6, 2024
Alzheimer's
disease
(AD)
is
a
major
neurodegenerative
disorder
that
courses
with
chronic
neuroinflammation.
Pleiotrophin
(PTN)
an
endogenous
inhibitor
of
Receptor
Protein
Tyrosine
Phosphatase
(RPTP)
β/ζ
which
upregulated
in
different
neuroinflammatory
disorders
diverse
origin,
including
AD.
To
investigate
the
role
RPTPβ/ζ
neuroinflammation
and
neurodegeneration,
we
used
eight-to
ten-month-old
APP/PS1
AD
mouse
model.
They
were
administered
intragastrically
MY10,
RPTPβ/ζ,
at
doses
(60
90
mg/kg)
every
day
for
14
days.
Treatment
mg/kg
MY10
significantly
reduced
number
size
amyloid
beta
(Aβ)
plaques
dorsal
subiculum
hippocampus
mice.
In
addition,
observed
significant
decrease
astrocytes
both
sexes
microglial
cells
sex-dependent
manner.
This
suggests
plays
important
modulating
Aβ
plaque
formation
influences
glial
responses,
may
contribute
to
improved
clearance.
treatment
decreased
interaction
Furthermore,
analysis
proinflammatory
markers
revealed
mRNA
levels
Language: Английский