Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

Ho, Shih‐Yin; Li, Lin; Chen, I‐Chun; Tsai, Che-Wen; Chang, Fang‐Chia; Liou, Horng-Huei

doi:10.3389/fphar.2021.682767

Cited by 9 publications

(3 citation statements)

References 39 publications

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“…Previous results reported similar observations using the same mouse model ( Scn1a A1783V on the pure C57BL/6J background, ( Pernici et al, 2021 )). Conversely, others that used DS mice with a mixed genetic background demonstrated a significantly increased seizure threshold ( Hawkins et al, 2017 ; Ho et al, 2021 ). Therefore, we repeated these experiments in Scn1a A1783V mice on a mixed C57BL/6J:129x1/SvJ background.…”

Section: Resultsmentioning

confidence: 99%

Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model

et al. 2023

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Dravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. Antiseizure medications (ASMs) for Dravet patients include valproic acid (VA) or clobazam (CLB), with or without stiripentol (STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. In addition to their effect on epileptic phenotypes, ASMs were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alterations in Dravet. Here, utilizing Dravet mice (DS, Scn1aA1783V/WT), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes. Compared to wild-type mice, background ECoG activity in DS mice had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, VA, CLB, or a combination of CLB + STP, caused, in most mice, a reduction in the frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes, with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands. Together, these data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations, and highlight a possible correlation between their effect on epilepsy and background activity.

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Section: Resultsmentioning

confidence: 99%

Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model

et al. 2023

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“…Previous results reported similar observations using the same mouse model (Scn1a A1783V on the pure C57BL/6J background) 23 . Conversely, others that used DS mice with a mixed genetic background demonstrated a significantly increased seizure threshold 19,28 . Therefore, we repeated these experiments in Scn1a A1783V mice on a mixed C57BL/6J:129x1/SvJ background.…”

Section: Reduced Background Ecog Power and Interhemispheric Coherence...mentioning

confidence: 98%

Acute effect of antiseizure drugs on background oscillations inScn1a^A1783VDravet syndrome mouse model

Quinn

Brusel

Ovadia

et al. 2022

Preprint

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Objective: Dravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. First-line treatment for DS patients includes valproic acid (VA) or clobazam with or without stiripentol (CLB+STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. As patients are rarely seizure-free, drug therapy focuses on reducing the seizure burden, as reported by caregivers. In addition to their effect on epileptic phenotypes, antiseizure medications (ASMs) were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alternations in Dravet. Methods: Utilizing Dravet mice (DS, Scn1aA1783V/WT), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes. Results: Compared to wild-type mice, background ECoG activity in DS had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, including VA or a combination of CLB+STP, caused, in most mice, a reduction of frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands. Significance: These data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations and highlight a possible correlation between their effect on epilepsy and background activity. Thus, examining these properties, following an acute administration, may be used as an additional tool for rapid evaluation of the therapeutic potential of ASMs.

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“… cond., conditional; sz, seizures. (1) Yu et al, 2006 , (2) Miller et al, 2014 , (3) Morey et al, 2022 , (4) Cheah et al, 2012 , (5) Jansen et al, 2020 , (6) Uchino et al, 2021 , (7) Ogiwara et al, 2013 , (8) Ogiwara et al, 2007 , (9) Tsai et al, 2015 , (10) Valassina et al, 2022 , (11) Dyment et al, 2020 , (12) Martin et al, 2010 , (13) Kuo et al, 2019 , (14) Ricobaraza et al, 2019 , (15) Voskobiynyk et al, 2021 , (16) Oakley et al, 2009 , (17) Hawkins et al, 2016 , (18) Hawkins et al, 2017 , (19) Gerbatin et al, 2022a , (20) Gerbatin et al, 2022b , (21) Satpute Janve et al, 2021 , (22) Anderson et al, 2022 , (23) Almog et al, 2021 , (24) Rubinstein et al, 2015 , (25) Nomura et al, 2019 , (26) Tanenhaus et al, 2022 , (27) Hawkins et al, 2021a , (28) Niibori et al, 2020 , (29) Williams et al, 2019 , (30) Chuang et al, 2021 , (31) Cao et al, 2012 , (32) Gheyara et al, 2014 , (33) Salgueiro-Pereira et al, 2019 , (34) Miljanovic et al, 2021 , (35) Cheah et al, 2021 , (36) Tran et al, 2020 , (37) Mattis et al, 2022 , (38) Kaneko et al, 2022 , (39) Yamagata et al, 2020 , (40) Ho et al, 2021 , (41) Hsiao et al, 2016 , (42) Mora-Jimenez et al, 2021 , (43) Pernici et al, 2021 , (44) Han et al, 2012 , (45) Hawkins et al, 2021a , (46) Ito et al, 2013 , (47) Fadila et al, 2020 , (48) Satta et al, 2021 , (49) Bahceci et al, 2020 , (50) …”

Section: Introductionunclassified

Heat-induced seizures, premature mortality, and hyperactivity in a novel Scn1a nonsense model for Dravet syndrome

Mavashov

Brusel

Liu³

et al. 2023

Front. Cell. Neurosci.

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Dravet syndrome (Dravet) is a severe congenital developmental genetic epilepsy caused by de novo mutations in the SCN1A gene. Nonsense mutations are found in ∼20% of the patients, and the R613X mutation was identified in multiple patients. Here we characterized the epileptic and non-epileptic phenotypes of a novel preclinical Dravet mouse model harboring the R613X nonsense Scn1a mutation. Scn1aWT/R613X mice, on a mixed C57BL/6J:129S1/SvImJ background, exhibited spontaneous seizures, susceptibility to heat-induced seizures, and premature mortality, recapitulating the core epileptic phenotypes of Dravet. In addition, these mice, available as an open-access model, demonstrated increased locomotor activity in the open-field test, modeling some non-epileptic Dravet-associated phenotypes. Conversely, Scn1aWT/R613X mice, on the pure 129S1/SvImJ background, had a normal life span and were easy to breed. Homozygous Scn1aR613X/R613X mice (pure 129S1/SvImJ background) died before P16. Our molecular analyses of hippocampal and cortical expression demonstrated that the premature stop codon induced by the R613X mutation reduced Scn1a mRNA and NaV1.1 protein levels to ∼50% in heterozygous Scn1aWT/R613X mice (on either genetic background), with marginal expression in homozygous Scn1aR613X/R613X mice. Together, we introduce a novel Dravet model carrying the R613X Scn1a nonsense mutation that can be used to study the molecular and neuronal basis of Dravet, as well as the development of new therapies associated with SCN1A nonsense mutations in Dravet.

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Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

Cited by 9 publications

References 39 publications

Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model

Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model

Acute effect of antiseizure drugs on background oscillations inScn1a^A1783VDravet syndrome mouse model

Heat-induced seizures, premature mortality, and hyperactivity in a novel Scn1a nonsense model for Dravet syndrome

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Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

Cited by 9 publications

References 39 publications

Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model

Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model

Acute effect of antiseizure drugs on background oscillations inScn1aA1783VDravet syndrome mouse model

Heat-induced seizures, premature mortality, and hyperactivity in a novel Scn1a nonsense model for Dravet syndrome

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Acute effect of antiseizure drugs on background oscillations inScn1a^A1783VDravet syndrome mouse model