Effects of repeated electroconvulsive shock seizures and pilocarpine-induced status epilepticus on emotional behavior in the rat

Cardoso, Armando; Carvalho, Liliana; Lukoyanova, Elena A.; Lukoyanov, Nikolay

doi:10.1016/j.yebeh.2008.11.004

Cited by 31 publications

(19 citation statements)

References 56 publications

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“…The current model of epilepsy is similar to previous studies3046 with minor modifications. The minimal current, duration, frequency, and interval required to produce a tonic-clonic seizure in the rat is strain-dependent4748.…”

Section: Methodssupporting

confidence: 57%

NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

Rothan

Amini

Faraj

et al. 2017

Sci Rep

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N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.

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Section: Methodssupporting

confidence: 57%

NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

Rothan

Amini

Faraj

et al. 2017

Sci Rep

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show abstract

“…In fact, the extended amygdala is involved in fear and anxiety responses [38,39], and TLE patients with ictal fear have atrophy of the amygdala [40]. Although high dose of pilocarpine in the experimental animals induces neuronal damage in the amygdaloid complex as shown in the present study, the relation between pilocarpine model of TLE and fear/anxiety response is controversial: high dose of pilocarpine reduces anxiety-like behavior and impair fear conditioning [41], increases anxiety-like behavior [42] or impairs extinction of fear memory with no differences in basic anxiety levels [43]. These conflicting results might depend on the severity of neuronal damage due to differences in experimental conditions, such as animal species (rat or mouse), strains of animals and doses of pilocarpine.…”

Section: Discussionmentioning

confidence: 91%

Increased Histone H3 Phosphorylation in Neurons in Specific Brain Structures after Induction of Status Epilepticus in Mice

et al. 2013

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Status epilepticus (SE) induces pathological and morphological changes in the brain. Recently, it has become clear that excessive neuronal excitation, stress and drug abuse induce chromatin remodeling in neurons, thereby altering gene expression. Chromatin remodeling is a key mechanism of epigenetic gene regulation. Histone H3 phosphorylation is frequently used as a marker of chromatin remodeling and is closely related to the upregulation of mRNA transcription. In the present study, we analyzed H3 phosphorylation levels in vivo using immunohistochemistry in the brains of mice with pilocarpine-induced SE. A substantial increase in H3 phosphorylation was detected in neurons in specific brain structures. Increased H3 phosphorylation was dependent on neuronal excitation. In particular, a robust upregulation of H3 phosphorylation was detected in the caudate putamen, and there was a gradient of phosphorylated H3+ (PH3+) neurons along the medio-lateral axis. After unilateral ablation of dopaminergic neurons in the substantia nigra by injection of 6-hydroxydopamine, the distribution of PH3+ neurons changed in the caudate putamen. Moreover, our histological analysis suggested that, in addition to the well-known MSK1 (mitogen and stress-activated kinase)/H3 phosphorylation/c-fos pathway, other signaling pathways were also activated. Together, our findings suggest that a number of genes involved in the pathology of epileptogenesis are upregulated in PH3+ brain regions, and that H3 phosphorylation is a suitable indicator of strong neuronal excitation.

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“…To test for abnormal locomotion and also for any effects on anxiety-like behavior, we performed open-field testing on epileptic animals treated with SP 28 μg/d; untreated, age-matched epileptic animals; and naive, age-matched controls. Prior studies have shown that increased anxiety-like behavior is a comorbidity of epilepsy induced in mice with pilocarpine or kainic acid (Muller et al, 2009; Liu et al, 2013), while decreased anxiety-like behavior is seen in pilocarpine-induced rats (Inostroza et al, 2012; Cardoso et al, 2009; Detour et al, 2005). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Antiepileptic action of c-Jun N-terminal kinase (JNK) inhibition in an animal model of temporal lobe epilepsy

et al. 2017

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Several phosphorylation signaling pathways have been implicated in the pathogenesis of epilepsy arising from both genetic causes and acquired insults to the brain. Identification of dysfunctional signaling pathways in epilepsy may provide novel targets for antiepileptic therapies. We previously described a deficit in phosphorylation signaling mediated by p38 mitogen-activated protein kinase (p38 MAPK) that occurs in an animal model of temporal lobe epilepsy, and that produces neuronal hyperexcitability measured in vitro. We asked whether in vivo pharmacological manipulation of p38 MAPK activity would influence seizure frequency in chronically epileptic animals. Administration of a p38 MAPK inhibitor, SB203580, markedly worsened spontaneous seizure frequency, consistent with prior in vitro results. However, anisomycin, a non-specific p38 MAPK activator, significantly increased seizure frequency. We hypothesized that this unexpected result was due to activation of a related MAPK, c-Jun N-terminal kinase (JNK). Administration of JNK inhibitor SP600125 significantly decreased seizure frequency in a dose-dependent manner without causing overt behavioral abnormalities. Biochemical analysis showed increased JNK expression and activity in untreated epileptic animals. These results show for the first time that JNK is hyperactivated in an animal model of epilepsy, and that phosphorylation signaling mediated by JNK may represent a novel antiepileptic target.

show abstract

Effects of repeated electroconvulsive shock seizures and pilocarpine-induced status epilepticus on emotional behavior in the rat

Cited by 31 publications

References 56 publications

NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

Increased Histone H3 Phosphorylation in Neurons in Specific Brain Structures after Induction of Status Epilepticus in Mice

Antiepileptic action of c-Jun N-terminal kinase (JNK) inhibition in an animal model of temporal lobe epilepsy

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