Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy
The interaction of Mesial Temporal Lobe Epilepsy (mTLE) with the circadian system control is apparent from an oscillatory pattern of limbic seizures, daytime's effect on seizure onset and the efficacy of antiepileptic drugs. Moreover, seizures per se can interfere with the biological rhythm out...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2018.00632/full |
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| author | Heloisa de Carvalho Matos Bruna Del Vechio Koike Wanessa dos Santos Pereira Tiago G. de Andrade Tiago G. de Andrade Olagide W. Castro Marcelo Duzzioni Maheedhar Kodali Joao P. Leite Ashok K. Shetty Daniel L. G. Gitaí Daniel L. G. Gitaí |
| author_facet | Heloisa de Carvalho Matos Bruna Del Vechio Koike Wanessa dos Santos Pereira Tiago G. de Andrade Tiago G. de Andrade Olagide W. Castro Marcelo Duzzioni Maheedhar Kodali Joao P. Leite Ashok K. Shetty Daniel L. G. Gitaí Daniel L. G. Gitaí |
| author_sort | Heloisa de Carvalho Matos |
| collection | DOAJ |
| description | The interaction of Mesial Temporal Lobe Epilepsy (mTLE) with the circadian system control is apparent from an oscillatory pattern of limbic seizures, daytime's effect on seizure onset and the efficacy of antiepileptic drugs. Moreover, seizures per se can interfere with the biological rhythm output, including circadian oscillation of body temperature, locomotor activity, EEG pattern as well as the transcriptome. However, the molecular mechanisms underlying this cross-talk remain unclear. In this study, we systematically evaluated the temporal expression of seven core circadian transcripts (Bmal1, Clock, Cry1, Cry2, Per1, Per2, and Per3) and the spontaneous locomotor activity (SLA) in post-status epilepticus (SE) model of mTLE. Twenty-four hour oscillating SLA remained intact in post-SE groups although the circadian phase and the amount and intensity of activity were changed in early post-SE and epileptic phases. The acrophase of the SLA rhythm was delayed during epileptogenesis, a fragmented 24 h rhythmicity and extended active phase length appeared in the epileptic phase. The temporal expression of circadian transcripts Bmal1, Cry1, Cry2, Per1, Per2, and Per3 was also substantially altered. The oscillatory expression of Bmal1 was maintained in rats imperiled to SE, but with lower amplitude (A = 0.2) and an advanced acrophase in the epileptic phase. The diurnal rhythm of Cry1 and Cry2 was absent in the early post-SE but was recovered in the epileptic phase. Per1 and Per2 rhythmic expression were disrupted in post-SE groups while Per3 presented an arrhythmic profile in the epileptic phase, only. The expression of Clock did not display rhythmic pattern in any condition. These oscillating patterns of core clock genes may contribute to hippocampal 24 h cycling and, consequently to seizure periodicity. Furthermore, by using a pool of samples collected at 6 different Zeitgeber Times (ZT), we found that all clock transcripts were significantly dysregulated after SE induction, except Per3 and Per2. Collectively, altered SLA rhythm in early post-SE and epileptic phases implies a possible role for seizure as a nonphotic cue, which is likely linked to activation of hippocampal–accumbens pathway. On the other hand, altered temporal expression of the clock genes after SE suggests their involvement in the MTLE. |
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| spelling | doaj.art-5f46545ff1fc4e0a99a3d34d1c3bbf962022-12-21T18:49:39ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-08-01910.3389/fneur.2018.00632342410Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe EpilepsyHeloisa de Carvalho Matos0Bruna Del Vechio Koike1Wanessa dos Santos Pereira2Tiago G. de Andrade3Tiago G. de Andrade4Olagide W. Castro5Marcelo Duzzioni6Maheedhar Kodali7Joao P. Leite8Ashok K. Shetty9Daniel L. G. Gitaí10Daniel L. G. Gitaí11Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, BrazilLaboratory of Molecular Chronobiology, Federal University of Alagoas, Arapiraca, BrazilDepartment of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, BrazilLaboratory of Molecular Chronobiology, Federal University of Alagoas, Arapiraca, BrazilDepartment of Physiology and Pharmacology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, BrazilInstitute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, United StatesInstitute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, United StatesDivision of Neurology, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, BrazilFaculty of Medicine, Federal University of Alagoas, Maceio, BrazilDivision of Neurology, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, BrazilDepartment of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, BrazilDivision of Neurology, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, BrazilThe interaction of Mesial Temporal Lobe Epilepsy (mTLE) with the circadian system control is apparent from an oscillatory pattern of limbic seizures, daytime's effect on seizure onset and the efficacy of antiepileptic drugs. Moreover, seizures per se can interfere with the biological rhythm output, including circadian oscillation of body temperature, locomotor activity, EEG pattern as well as the transcriptome. However, the molecular mechanisms underlying this cross-talk remain unclear. In this study, we systematically evaluated the temporal expression of seven core circadian transcripts (Bmal1, Clock, Cry1, Cry2, Per1, Per2, and Per3) and the spontaneous locomotor activity (SLA) in post-status epilepticus (SE) model of mTLE. Twenty-four hour oscillating SLA remained intact in post-SE groups although the circadian phase and the amount and intensity of activity were changed in early post-SE and epileptic phases. The acrophase of the SLA rhythm was delayed during epileptogenesis, a fragmented 24 h rhythmicity and extended active phase length appeared in the epileptic phase. The temporal expression of circadian transcripts Bmal1, Cry1, Cry2, Per1, Per2, and Per3 was also substantially altered. The oscillatory expression of Bmal1 was maintained in rats imperiled to SE, but with lower amplitude (A = 0.2) and an advanced acrophase in the epileptic phase. The diurnal rhythm of Cry1 and Cry2 was absent in the early post-SE but was recovered in the epileptic phase. Per1 and Per2 rhythmic expression were disrupted in post-SE groups while Per3 presented an arrhythmic profile in the epileptic phase, only. The expression of Clock did not display rhythmic pattern in any condition. These oscillating patterns of core clock genes may contribute to hippocampal 24 h cycling and, consequently to seizure periodicity. Furthermore, by using a pool of samples collected at 6 different Zeitgeber Times (ZT), we found that all clock transcripts were significantly dysregulated after SE induction, except Per3 and Per2. Collectively, altered SLA rhythm in early post-SE and epileptic phases implies a possible role for seizure as a nonphotic cue, which is likely linked to activation of hippocampal–accumbens pathway. On the other hand, altered temporal expression of the clock genes after SE suggests their involvement in the MTLE.https://www.frontiersin.org/article/10.3389/fneur.2018.00632/fullclock genesepilepsyseizurespontaneous locomotor activitycircadian rhythm |
| spellingShingle | Heloisa de Carvalho Matos Bruna Del Vechio Koike Wanessa dos Santos Pereira Tiago G. de Andrade Tiago G. de Andrade Olagide W. Castro Marcelo Duzzioni Maheedhar Kodali Joao P. Leite Ashok K. Shetty Daniel L. G. Gitaí Daniel L. G. Gitaí Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy Frontiers in Neurology clock genes epilepsy seizure spontaneous locomotor activity circadian rhythm |
| title | Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy |
| title_full | Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy |
| title_fullStr | Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy |
| title_full_unstemmed | Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy |
| title_short | Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy |
| title_sort | rhythms of core clock genes and spontaneous locomotor activity in post status epilepticus model of mesial temporal lobe epilepsy |
| topic | clock genes epilepsy seizure spontaneous locomotor activity circadian rhythm |
| url | https://www.frontiersin.org/article/10.3389/fneur.2018.00632/full |
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