Different types of cell death are involved in brain damage of methylmalonic aciduria and glutaric aciduria type I
Details
Serval ID
serval:BIB_B9F0E4283B3A
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
Different types of cell death are involved in brain damage of methylmalonic aciduria and glutaric aciduria type I
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
S170-S171
Language
english
Abstract
We previously showed that exposure of 3D organotypic rat brain cell
cultures to 1mM 2-methylcitrate (2-MCA) or 3-hydroxyglutarate (3-
OHGA) every 12h over three days (DIV11-DIV14) results in ammonium
accumulation and cell death. The aim of this study was to define the
time course (every 24h) of the observed effects.
Ammonium in culture medium already increased at DIV12 staying
stable on the following days under 3-OHGA exposure, while it increased
consecutively up to much higher levels under 2-MCA
exposure. Lactate increase and glucose decrease were observed from
DIV13 and DIV14, respectively. We conclude that ammonium accumulation
precedes alterations of energy metabolism.
As observed by immunohistochemistry glial cells were the predominant
dying cells. Immunoblotting and immunohistochemistry with cell death
specific markers (caspase-3, alpha-fodrin, LC3) showed that 2-MCA
exposure significantly increased apoptosis on DIV14, but did not alter
autophagy or necrosis. In contrast, 3-OHGA exposure substantially
increased necrosis already from DIV13, while no change was observed
for apoptosis and autophagy.
In conclusion, ammonium accumulation, secondary disturbance of energy
metabolism and glial cell death are involved in the neuropathogenesis
ofmethylmalonic aciduria and glutaric aciduria type I. Interestingly, brain
cells are dying by necrosis under 3-OHGA exposure and by apoptosis
under 2-MCA exposure.
cultures to 1mM 2-methylcitrate (2-MCA) or 3-hydroxyglutarate (3-
OHGA) every 12h over three days (DIV11-DIV14) results in ammonium
accumulation and cell death. The aim of this study was to define the
time course (every 24h) of the observed effects.
Ammonium in culture medium already increased at DIV12 staying
stable on the following days under 3-OHGA exposure, while it increased
consecutively up to much higher levels under 2-MCA
exposure. Lactate increase and glucose decrease were observed from
DIV13 and DIV14, respectively. We conclude that ammonium accumulation
precedes alterations of energy metabolism.
As observed by immunohistochemistry glial cells were the predominant
dying cells. Immunoblotting and immunohistochemistry with cell death
specific markers (caspase-3, alpha-fodrin, LC3) showed that 2-MCA
exposure significantly increased apoptosis on DIV14, but did not alter
autophagy or necrosis. In contrast, 3-OHGA exposure substantially
increased necrosis already from DIV13, while no change was observed
for apoptosis and autophagy.
In conclusion, ammonium accumulation, secondary disturbance of energy
metabolism and glial cell death are involved in the neuropathogenesis
ofmethylmalonic aciduria and glutaric aciduria type I. Interestingly, brain
cells are dying by necrosis under 3-OHGA exposure and by apoptosis
under 2-MCA exposure.
Create date
14/02/2014 17:59
Last modification date
20/08/2019 15:27
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