Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro
The creatine precursor Guanidinoacetic Acid (GAA) accumulates in the genetic deficiency of the GuanidinoAcetate Methyl Transferase (GAMT) enzyme and it is believed to cause the seizures that often occur in this condition. However, evidence that it is indeed epileptogenic is scarce and we previously...
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MDPI AG
2022-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/1/74 |
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| author | Fabio Poggio Martina Brofiga Mariateresa Tedesco Paolo Massobrio Enrico Adriano Maurizio Balestrino |
| author_facet | Fabio Poggio Martina Brofiga Mariateresa Tedesco Paolo Massobrio Enrico Adriano Maurizio Balestrino |
| author_sort | Fabio Poggio |
| collection | DOAJ |
| description | The creatine precursor Guanidinoacetic Acid (GAA) accumulates in the genetic deficiency of the GuanidinoAcetate Methyl Transferase (GAMT) enzyme and it is believed to cause the seizures that often occur in this condition. However, evidence that it is indeed epileptogenic is scarce and we previously found that it does not cause neuronal hyperexcitation in in vitro brain slices. Here, we used Micro-Electrode Arrays (MEAs) to further investigate the electrophysiological effects of its acute and chronic administration in the networks of cultured neurons, either neocortical or hippocampal. We found that: (1) GAA at the 1 µM concentration, comparable to its concentration in normal cerebrospinal fluid, does not modify any of the parameters we investigated in either neuronal type; (2) at the 10 µM concentration, very similar to that found in the GAMT deficiency, it did not affect any of the parameters we tested except the bursting rate of neocortical networks and the burst duration of hippocampal networks, both of which were decreased, a change pointing in a direction opposite to epileptogenesis; (3) at the very high and unphysiological 100 µM concentration, it caused a decrease in all parameters, a change that again goes in the direction opposite to epileptogenesis. Our results confirm that GAA is not epileptogenic. |
| first_indexed | 2024-03-09T13:27:17Z |
| format | Article |
| id | doaj.art-712142eef1b84eecb0d6ad0d0096d16a |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T13:27:17Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-712142eef1b84eecb0d6ad0d0096d16a2023-11-30T21:22:21ZengMDPI AGBiomolecules2218-273X2022-12-011317410.3390/biom13010074Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In VitroFabio Poggio0Martina Brofiga1Mariateresa Tedesco2Paolo Massobrio3Enrico Adriano4Maurizio Balestrino5Department of Informatics, Bioengineering, Robotics, and Systems Engineering (DIBRIS), University of Genova, 16145 Genova, ItalyDepartment of Informatics, Bioengineering, Robotics, and Systems Engineering (DIBRIS), University of Genova, 16145 Genova, Italy3Brain Gmbh, 8820 Wadenswil, SwitzerlandDepartment of Informatics, Bioengineering, Robotics, and Systems Engineering (DIBRIS), University of Genova, 16145 Genova, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Sciences (DINOGMI), University of Genoa, 16145 Genova, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Sciences (DINOGMI), University of Genoa, 16145 Genova, ItalyThe creatine precursor Guanidinoacetic Acid (GAA) accumulates in the genetic deficiency of the GuanidinoAcetate Methyl Transferase (GAMT) enzyme and it is believed to cause the seizures that often occur in this condition. However, evidence that it is indeed epileptogenic is scarce and we previously found that it does not cause neuronal hyperexcitation in in vitro brain slices. Here, we used Micro-Electrode Arrays (MEAs) to further investigate the electrophysiological effects of its acute and chronic administration in the networks of cultured neurons, either neocortical or hippocampal. We found that: (1) GAA at the 1 µM concentration, comparable to its concentration in normal cerebrospinal fluid, does not modify any of the parameters we investigated in either neuronal type; (2) at the 10 µM concentration, very similar to that found in the GAMT deficiency, it did not affect any of the parameters we tested except the bursting rate of neocortical networks and the burst duration of hippocampal networks, both of which were decreased, a change pointing in a direction opposite to epileptogenesis; (3) at the very high and unphysiological 100 µM concentration, it caused a decrease in all parameters, a change that again goes in the direction opposite to epileptogenesis. Our results confirm that GAA is not epileptogenic.https://www.mdpi.com/2218-273X/13/1/74guanidinoacetic acidcreatineGAMT deficiencyseizuresepilepsyelectrophysiology |
| spellingShingle | Fabio Poggio Martina Brofiga Mariateresa Tedesco Paolo Massobrio Enrico Adriano Maurizio Balestrino Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro Biomolecules guanidinoacetic acid creatine GAMT deficiency seizures epilepsy electrophysiology |
| title | Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro |
| title_full | Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro |
| title_fullStr | Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro |
| title_full_unstemmed | Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro |
| title_short | Lack of Epileptogenic Effects of the Creatine Precursor Guanidinoacetic Acid on Neuronal Cultures In Vitro |
| title_sort | lack of epileptogenic effects of the creatine precursor guanidinoacetic acid on neuronal cultures in vitro |
| topic | guanidinoacetic acid creatine GAMT deficiency seizures epilepsy electrophysiology |
| url | https://www.mdpi.com/2218-273X/13/1/74 |
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