Cell Signaling Underlying Epileptic Behavior

Bozzi, Yuri; Dunleavy, Mark; Henshall, David C.

doi:10.3389/fnbeh.2011.00045

Cited by 71 publications

(60 citation statements)

References 165 publications

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“…These markers have been found to be widely expressed in the hippocampus of animals exposed to seizures induced by kainate (Kim et al, 1994; Crespo-Biel et al, 2007), pilocarpine (Garrido et al, 1998; Berkeley et al, 2002; Houser et al, 2008), bicuculline (Gass et al, 1993; Ben et al, 2014), and dopamine D 1 receptor agonists (Bozzi et al, 2011; Gangarossa et al, 2011, 2014; Bozzi and Borrelli, 2013). We also found p-ERK1/2 to be induced by audiogenic seizures in mice affected by fragile X syndrome (Curia et al, 2013) and, interestingly, changes in p-ERK1/2 have been associated to a different sensitivity to proconvulsant stimuli (Glazova et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

Giordano

Costa

Lucchi

et al. 2016

Front. Cell. Neurosci.

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The 6-Hz corneal stimulation test is used to screen novel antiepileptic molecules to overcome the problem of drug refractoriness. Although recognized as a standard test, it has been evaluated only recently in the attempt to characterize the putative neuronal networks involved in seizures caused by corneal stimulation. In particular, by recording from the CA1 region we previously established that the hippocampus participates to propagation of seizure activity. However, these findings were not corroborated by using markers of neuronal activation such as FosB/ΔFosB antigens. In view of this discrepancy, we performed new experiments to characterize the changes in levels of phosphorylated extracellular signal-regulated kinases1/2 (p-ERK1/2), which are also used as markers of neuronal activation. To this aim, mice underwent corneal stimulation up to three different times, in three sessions separated by an interval of 3 days. To characterize a group in which seizures could be prevented by pharmacological treatment, we also considered pretreatment with the ghrelin receptor antagonist EP-80317 (330 μg/kg). Control mice were sham-treated. Video electrocorticographic (ECoG) recordings were obtained from mice belonging to each group of treatment. Animals were finally used to characterize the immunoreactivity for FosB/ΔFosB and p-ERK1/2 in the hippocampus. As previously shown, FosB/ΔFosB levels were highly increased throughout the hippocampus by the first induced seizure but, in spite of the progressively increased seizure severity, they were restored to control levels after the third stimulation. At variance, corneal stimulation caused a progressive increase in p-ERK1/2 immunoreactivity all over the hippocampus, especially in CA1, peaking in the third session. Predictably, EP-80317 administration reduced both duration and severity of seizures, prevented the increase in FosB/ΔFosB levels in the first session, and partially counteracted the increase in p-ERK1/2 levels in the third session. The vast majority of p-ERK1/2 immunopositive cells were co-labeled with FosB/ΔFosB antibodies, suggesting the existence of a relationship between the investigated markers in a subpopulation of neurons activated by seizures. These findings suggest that p-ERK1/2 are useful markers to define the aggravation of seizures and the response to anticonvulsant treatments. In particular, p-ERK1/2 expression clearly identified the involvement of hippocampal regions during seizure aggravation in the 6-Hz model.

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Section: Introductionmentioning

confidence: 99%

Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

Giordano

Costa

Lucchi

et al. 2016

Front. Cell. Neurosci.

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“…The AKT1 gene is an attractive candidate because it codes for a protein kinase that forms an integral part of the dopamine receptor signaling cascade in the striatum (9). Moreover, in vivo administration to mice of delta-9-tetrahydrocannabinol (delta-9-TCH), the active ingredient in cannabis, activates this signaling cascade via AKT1 phosphorylation (10,11).…”

mentioning

confidence: 99%

Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users

Forti

Iyegbe

Sallis

et al. 2012

Biological Psychiatry

208

156

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“…The prototypical and most characterized immediate early gene-encoded transcription factor is c-Fos which is expressed with a peak of 30 to 90 minutes after stimulation (Herrera and Robertson, 1996). There is ample literature describing neuronal c-Fos induction following kindling and other seizure models (Barone et al, 1993; Bozzi et al, 2011; Chiasson et al, 1995; Dragunow and Faull, 1989; Dragunow and Robertson, 1988; Morgan and Curran, 1991a, b; Motte et al, 1997). Furthermore, several studies have demonstrated a correlation between the expansion of c-Fos induction from limbic areas to the cerebral cortex and the progression of epileptic seizures (Andre et al, 1998; Clark et al, 1991; Ebert and Loscher, 1995; Hiscock et al, 2001; Simler et al, 1999; Szyndler et al, 2009; Willoughby et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition

Albright

Dhaher

Wang

et al. 2017

Experimental Neurology

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Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE). However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats. We then used continuous video-intracranial electroencephalogram (EEG) monitoring and c-Fos immunohistochemistry to determine the type of seizures and spatial distribution of neuronal activation early (1–5 days postinfusion) and late (16–43 days postinfusion) in epileptogenesis. Early in epileptogenesis, seizures were preferentially mild (stage 1–2), activating neurons in the entorhinal-hippocampal area, the basolateral amygdala, the piriform cortex, the midline thalamus, and the anterior olfactory area. Late in epileptogenesis, the seizures were generally more severe (stage 4–5) with neuronal activation extending to the neocortex, the bed nucleus of the stria terminalis, the mediodorsal thalamus, and the central nucleus of the amygdala. Our findings demonstrate that inhibition of GS focally in the hippocampal formation triggers a process of epileptogenesis characterized by gradual worsening of seizure severity and involvement of progressively larger neuronal populations over a period of several weeks. Knowledge about the underlying mechanism of epileptogenesis is important because such knowledge may result in more specific and efficacious treatments of MTLE by moving away from large and poorly specific surgical resections to highly targeted surgical or pharmacological interventions of the epileptogenic process.

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Cell Signaling Underlying Epileptic Behavior

Cited by 71 publications

References 165 publications

Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users

Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition

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