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MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway.
[congenital toxoplasmosis]
Congenital
toxoplasmosis
and
toxoplasmic
encephalitis
can
be
associated
with
severe
neuropsychiatric
symptoms
.
However
,
which
host
cell
processes
are
regulated
and
how
Toxoplasma
gondii
affects
these
changes
remain
unclear
.
MicroRNAs
(
miRNAs
)
are
small
noncoding
RNA
sequences
critical
to
neurodevelopment
and
adult
neuronal
processes
by
coordinating
the
activity
of
multiple
genes
within
biological
networks
.
We
examined
the
expression
of
over
1000
miRNAs
in
human
neuroepithelioma
cells
in
response
to
infection
with
Toxoplasma
.
MiR-
132
,
a
cyclic
AMP
-responsive
element
binding
(
CREB
)
-
regulated
miRNA
,
was
the
only
miRNA
that
was
substantially
upregulated
by
all
three
prototype
Toxoplasma
strains
.
The
increased
expression
of
miR-
132
was
also
documented
in
mice
following
infection
with
Toxoplasma
.
To
identify
cellular
pathways
regulated
by
miR-
132
,
we
performed
target
prediction
followed
by
pathway
enrichment
analysis
in
the
transcriptome
of
Toxoplasma-infected
mice
.
This
led
us
to
identify
20
genes
and
dopamine
receptor
signaling
was
their
strongest
associated
pathway
.
We
then
examined
myriad
aspects
of
the
dopamine
pathway
in
the
striatum
of
Toxoplasma-infected
mice
5
days
after
infection
.
Here
we
report
decreased
expression
of
D
1
-
like
dopamine
receptors
(
DRD
1
,
DRD
5
)
,
metabolizing
enzyme
(
MAOA
)
and
intracellular
proteins
associated
with
the
transduction
of
dopamine-mediated
signaling
(
DARPP-
32
phosphorylation
at
Thr
34
and
Ser
97
)
.
Increased
concentrations
of
dopamine
and
its
metabolites
,
serotonin
(
5
-
HT
)
and
5
-
hydroxyindoleacetic
acid
were
documented
by
HPLC
analysis
;
however
,
the
metabolism
of
dopamine
was
decreased
and
5
-
HT
metabolism
was
unchanged
.
Our
data
show
that
miR-
132
is
upregulated
following
infection
with
Toxoplasma
and
is
associated
with
changes
in
dopamine
receptor
signaling
.
Our
findings
provide
a
possible
mechanism
for
how
the
parasite
contributes
to
the
neuropathology
of
infection
.
Diseases
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"then examined myriad aspects of the dopamine pathway in the striatum"
symptom
congenital toxoplasmosis
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