NDLI: Disturbance of the glutamatergic system by glutaric acid in striatum and cerebral cortex of glutaryl-CoA dehydrogenase-deficient knockout mice: Possible implications for the neuropathology of glutaric acidemia type I

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Disturbance of the glutamatergic system by glutaric acid in striatum and cerebral cortex of glutaryl-CoA dehydrogenase-deficient knockout mice: Possible implications for the neuropathology of glutaric acidemia type I

Content Provider	Semantic Scholar
Author	Busanello, Estela Natacha Brandt Fernandes, Carolina Gonçalves Martell, Rafael Volter Lobato, Vannessa Gonçalves Araujo Wajner, Moacir
Copyright Year	2014
Abstract	The role of excitotoxicity on the neuropathology of glutaric acidemia type I (GA I) is still under debate. Therefore, in the present work, we evaluated glutamate uptake by brain slices and glutamate binding to synaptic membranes, as well as glutamine synthetase activity in cerebral cortex and striatum from glutaryl-CoA dehydrogenase deficient (Gcdh(-/-)) mice along development (7, 15, 30 and 60 days of life) in the hopes of clarifying this matter. We also tested the influence of glutaric acid (GA) added exogenously on these parameters. [(3)H]Glutamate uptake was not significantly altered in cerebral cortex and striatum from Gcdh(-/-) mice, as compared to WT mice. However, GA provoked a significant decrease of [(3)H]glutamate uptake in striatum from both WT and Gcdh(-/-) mice older than 7 days. This inhibitory effect was more pronounced in Gcdh(-/-), as compared to WT mice. The use of a competitive inhibitor of glutamate astrocytic transporters indicated that the decrease of [(3)H]glutamate uptake caused by GA was due to the competition between this organic acid and glutamate for the same astrocytic transporter site. We also found that Na(+)-dependent [(3)H]glutamate binding (binding to transporters) was increased in the striatum from Gcdh(-/-) mice and that GA significantly diminished this binding both in striatum and cerebral cortex from Gcdh(-/-), but not from WT mice. Finally, we observed that glutamine synthetase activity was not changed in brain cortex and striatum from Gcdh(-/-) and WT mice and that GA was not able to alter this activity. It is therefore presumed that a disturbance of the glutamatergic neurotransmission system caused by GA may potentially be involved in the neuropathology of GA I, particularly in the striatum.
Starting Page	260
Ending Page	267
Page Count	8
File Format	PDF HTM / HTML
DOI	10.1016/j.jns.2014.09.003
PubMed reference number	25241940
Journal	Medline
Volume Number	346
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S0022510X14005826
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S0022510X14005826?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/j.jns.2014.09.003
Journal	Journal of the Neurological Sciences
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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Glutaric acidemia type ii (gaii) references.

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