Circadian variation in anticonvulsant activity of valproic acid in mice

Khedhaier, Wafa Ben Cherif; Dridi, Ichrak; Aouam, Karim; Ben‐Attia, Mossadok; Reinberg, A; Boughattas, Naceur A.

doi:10.1016/j.biopha.2017.08.047

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…On the other hand, the circadian products oscillation in an epileptic hippocampus may contribute to rhythmic variation in the epilepsy threshold, and generation of SRS in a temporal pattern. In fact, it has been shown that the daytime or dark/light conditions influence the susceptibility for seizure onset and severity ( 51 – 53 , 80 ) as well as the anticonvulsant efficacy of antiepileptic drugs ( 81 ). Thus, the oscillatory gene can drive a circadian availability of molecular factors that act in the electrical activity of the brain, resulting in rhythmic fluctuation in neuronal excitability ( 23 , 82 ).…”

Section: Discussionmentioning

confidence: 99%

Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy

et al. 2018

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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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Section: Discussionmentioning

confidence: 99%

Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy

et al. 2018

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“…The viability of chronotherapeutic strategies to optimize the efficacy of anti-epileptic drug (AED) treatment is supported by both clinical and basic research. In a study with rodents, the anti-convulsant efficacy of valproic acid varied as a function of the time in which it was administered (184). Though valproic acid increased the latency to the first pentylnetetrazol-induced seizure at all time points, the highest and lowest increases were observed when the drug was administered 7 and 19 h after light onset, respectively.…”

Section: Chronotherapy In Epilepsymentioning

confidence: 99%

The Molecular Genetic Interaction Between Circadian Rhythms and Susceptibility to Seizures and Epilepsy

Batterman

Gerstner

et al. 2020

Front. Neurol.

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Seizure patterns observed in patients with epilepsy suggest that circadian rhythms and sleep/wake mechanisms play some role in the disease. This review addresses key topics in the relationship between circadian rhythms and seizures in epilepsy. We present basic information on circadian biology, but focus on research studying the influence of both the time of day and the sleep/wake cycle as independent but related factors on the expression of seizures in epilepsy. We review studies investigating how seizures and epilepsy disrupt expression of core clock genes, and how disruption of clock mechanisms impacts seizures and the development of epilepsy. We focus on the overlap between mechanisms of circadian-associated changes in SCN neuronal excitability and mechanisms of epileptogenesis as a means of identifying key pathways and molecules that could represent new targets or strategies for epilepsy therapy. Finally, we review the concept of chronotherapy and provide a perspective regarding its application to patients with epilepsy based on their individual characteristics (i.e., being a "morning person" or a "night owl"). We conclude that better understanding of the relationship between circadian rhythms, neuronal excitability, and seizures will allow both the identification of new therapeutic targets for treating epilepsy as well as more effective treatment regimens using currently available pharmacological and non-pharmacological strategies.

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“…Still, the highest anticonvulsant activity was also achieved at ZT 7, despite lower plasma AUC and higher clearance. The authors suggest that the dose required for optimal prevention of epileptic seizures may be lower in rest period than during activity (Khedhaier et al, 2017), but it would have been relevant to monitor drug concentrations at the biophase (i.e., brain), in addition to PK parameters in plasma.…”

Section: Chronopharmacokinetics: Non‐clinical Datamentioning

confidence: 99%

Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics

Bicker

Alves

Falcão

2020

British J Pharmacology

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The importance of drug dosing time in pharmacokinetics, pharmacodynamics, and toxicity is receiving increasing attention from the scientific community. In spite of mounting evidence that circadian oscillations affect drug absorption, distribution, metabolism, and excretion (ADME), there remain many unanswered questions in this field and, occasionally, conflicting experimental results. Such data arise not only from translational difficulties caused by interspecies differences but also from variability in study design and a lack of understanding of how the circadian clock affects physiological factors that strongly influence ADME, namely, the expression and activity of drug transporters. Hence, the main goal of this review is to provide an updated analysis of the role of the circadian rhythm in drug absorption, distribution across bloodtissue barriers, metabolism in hepatic and extra-hepatic tissues, and hepatobiliary and renal excretion. It is expected that the research suggestions proposed here will contribute to a tissue-targeted and time-targeted pharmacotherapy.

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Circadian variation in anticonvulsant activity of valproic acid in mice

Cited by 7 publications

References 38 publications

Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy

Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status Epilepticus Model of Mesial Temporal Lobe Epilepsy

The Molecular Genetic Interaction Between Circadian Rhythms and Susceptibility to Seizures and Epilepsy

Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics

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