Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Impaired glutamatergic synaptic transmission in the PKU brain.
[classical phenylketonuria]
This
paper
reviews
recent
results
of
our
investigation
of
the
mechanisms
whereby
hyperphenylalaninemia
may
cause
brain
dysfunction
in
classical
phenylketonuria
(
PKU
)
.
Acute
applications
of
L-Phe
in
rat
and
mouse
hippocampal
and
cerebrocortical
cultured
neurons
,
at
a
range
of
concentrations
found
in
PKU
brain
,
significantly
and
reversibly
depressed
glutamatergic
synaptic
transmission
by
a
combination
of
pre-
and
postsynaptic
actions
:
(
1
)
competition
for
the
glycine-binding
site
of
the
N-
methyl-
D-
aspartate
(
NMDA
)
receptors
;
(
2
)
attenuation
of
neurotransmitter
release
;
(
3
)
competition
for
the
glutamate-binding
site
of
(
RS
)
-
amino-
3
-
hydroxy-
5
-
methyl-
4
-
isoxazolepropioinic
acid
and
kainate
(
AMPA
/
kainate
)
receptors
.
Unlike
L-Phe
,
its
non-tyrosine
metabolites
,
phenylacetic
acid
,
phenylpyruvic
acid
,
and
phenyllactic
acid
,
did
not
produce
antiglutamatergic
effects
.
L-Phe
did
not
affect
inhibitory
gamma-aminobutyric
(
GABA
)
-
ergic
transmission
.
Consistent
with
this
specific
pattern
of
effects
caused
by
L-Phe
in
neuronal
cultures
,
the
expression
of
NMDA
receptor
NR
2
A
and
AMPA
receptor
Glu
1
and
Glu
2
/
3
subunits
in
brain
of
hyperphenylalaninemic
PKU
mice
(
Pah
(
enu
2
)
strain
)
was
significantly
increased
,
whereas
expression
of
the
NMDA
receptor
NR
2
B
subunit
was
decreased
.
There
was
no
change
in
GABA
alpha
1
subunit
expression
.
Considering
the
important
role
of
glutamatergic
synaptic
transmission
in
normal
brain
development
and
function
,
these
L-Phe-induced
changes
in
glutamatergic
synaptic
transmission
in
PKU
brain
may
be
a
critical
element
of
the
neurological
symptoms
of
PKU
.
Diseases
Validation
Diseases presenting
"the expression of nmda receptor nr2a and ampa receptor glu1 and glu2"
symptom
classical phenylketonuria
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom