Low concentrations of 3-hydroxy glutarate leads to ammonium accumulation and non-apoptotic cell death in developing brain cells
Details
Serval ID
serval:BIB_F9F3659511D3
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Poster: Summary – with images – on one page of the results of a researche project. The summaries of the poster must be entered in "Abstract" and not "Poster".
Collection
Publications
Institution
Title
Low concentrations of 3-hydroxy glutarate leads to ammonium accumulation and non-apoptotic cell death in developing brain cells
Title of the conference
ICIEM 2013, 12th International Congress of Inborn Errors of Metabolism
Address
Barcelona, Spain, September 3-6, 2013
ISBN
0141-8955
Publication state
Published
Issued date
2013
Volume
36
Series
Journal of Inherited Metabolic Diseases
Pages
S173
Language
english
Abstract
We previously showed in a 3D rat brain cell in vitro model for glutaric
aciduria type-I that repeated application of 1mM 3-hydroxy-glutarate
(3-OHGA) caused ammonium accumulation, morphologic alterations
and induction of non-apoptotic cell death in developing brain cells.
Here, we performed a dose-response study with lower concentrations of 3-
OHGA.We exposed our cultures to 0.1, 0.33 and 1mM 3-OHGA every 12h
over three days at two developmental stages (DIV5-8 and DIV11-14).
Ammonium accumulation was observed at both stages starting from
0.1mM 3-OHGA, in parallel with a glutamine decrease. Morphological
changes started at 0.33mM with loss of MBP expression and loss of
astrocytic processes. Neurons were not substantially affected. At DIV8,
release of LDH in the medium and cellular TUNEL staining increased
from 0.1mM and 0.33mM 3-OHGA exposure, respectively. No increase
in activated caspase-3 was observed.
We confirmed ammonium accumulation and non-apoptotic cell
death of brain cells in our in vitro model at lower 3-OHGA
concentrations thus strongly suggesting that the observed effects
are likely to take place in the brain of affected patients. The
concomitant glutamine decrease suggests a defect in the astrocyte
ammonium buffering system. Ammonium accumulation might be
the cause of non-apoptotic cell death.
aciduria type-I that repeated application of 1mM 3-hydroxy-glutarate
(3-OHGA) caused ammonium accumulation, morphologic alterations
and induction of non-apoptotic cell death in developing brain cells.
Here, we performed a dose-response study with lower concentrations of 3-
OHGA.We exposed our cultures to 0.1, 0.33 and 1mM 3-OHGA every 12h
over three days at two developmental stages (DIV5-8 and DIV11-14).
Ammonium accumulation was observed at both stages starting from
0.1mM 3-OHGA, in parallel with a glutamine decrease. Morphological
changes started at 0.33mM with loss of MBP expression and loss of
astrocytic processes. Neurons were not substantially affected. At DIV8,
release of LDH in the medium and cellular TUNEL staining increased
from 0.1mM and 0.33mM 3-OHGA exposure, respectively. No increase
in activated caspase-3 was observed.
We confirmed ammonium accumulation and non-apoptotic cell
death of brain cells in our in vitro model at lower 3-OHGA
concentrations thus strongly suggesting that the observed effects
are likely to take place in the brain of affected patients. The
concomitant glutamine decrease suggests a defect in the astrocyte
ammonium buffering system. Ammonium accumulation might be
the cause of non-apoptotic cell death.
Create date
14/02/2014 19:01
Last modification date
20/08/2019 17:25
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