Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model
The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor...
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MDPI AG
2021-07-01
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| author | Vasily A. Aleshin Anastasia V. Graf Artem V. Artiukhov Alexandra I. Boyko Alexander L. Ksenofontov Maria V. Maslova Isabel Nogués Martino L. di Salvo Victoria I. Bunik |
| author_facet | Vasily A. Aleshin Anastasia V. Graf Artem V. Artiukhov Alexandra I. Boyko Alexander L. Ksenofontov Maria V. Maslova Isabel Nogués Martino L. di Salvo Victoria I. Bunik |
| author_sort | Vasily A. Aleshin |
| collection | DOAJ |
| description | The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications. |
| first_indexed | 2024-03-10T08:29:49Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T08:29:49Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-f9a0968204bc444d8af13175f4f576c42023-11-22T09:11:01ZengMDPI AGPharmaceuticals1424-82472021-07-0114873710.3390/ph14080737Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat ModelVasily A. Aleshin0Anastasia V. Graf1Artem V. Artiukhov2Alexandra I. Boyko3Alexander L. Ksenofontov4Maria V. Maslova5Isabel Nogués6Martino L. di Salvo7Victoria I. Bunik8Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, RussiaFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, RussiaA.N. Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaFaculty of Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaResearch Institute of Terrestrial Ecosystems, National Research Council, Via Salaria km 29.300, Monterotondo, 00015 Rome, ItalyDepartment of Biological Sciences A. Rossi Fanelli, Sapienza University, 00185 Rome, ItalyFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, RussiaThe disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.https://www.mdpi.com/1424-8247/14/8/737amino acid neurotransmitterglutamateGABApentylenetetrazolevitamin B1vitamin B6 |
| spellingShingle | Vasily A. Aleshin Anastasia V. Graf Artem V. Artiukhov Alexandra I. Boyko Alexander L. Ksenofontov Maria V. Maslova Isabel Nogués Martino L. di Salvo Victoria I. Bunik Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model Pharmaceuticals amino acid neurotransmitter glutamate GABA pentylenetetrazole vitamin B1 vitamin B6 |
| title | Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model |
| title_full | Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model |
| title_fullStr | Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model |
| title_full_unstemmed | Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model |
| title_short | Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model |
| title_sort | physiological and biochemical markers of the sex specific sensitivity to epileptogenic factors delayed consequences of seizures and their response to vitamins b1 and b6 in a rat model |
| topic | amino acid neurotransmitter glutamate GABA pentylenetetrazole vitamin B1 vitamin B6 |
| url | https://www.mdpi.com/1424-8247/14/8/737 |
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