Cellular mechanisms of cobalt‐induced hippocampal epileptiform discharges

He, Jiwen; Hsiang, Hwa-Lin Liz; Wu, Chenggang; Mylvagnanam, Shanthini; Carlen, Peter L.; Zhang, Liang

doi:10.1111/j.1528-1167.2008.01767.x

Cited by 41 publications

(20 citation statements)

References 73 publications

(111 reference statements)

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“…However, for patients with focal cortical dysplasia lesions, the authors found a positive correlation between Panx1 expression levels and the frequency of seizures that the patients had before surgery [73], suggesting the involvement of Panx1 in the epileptogenic process. Similar upregulation of Panx1 expression levels were obtained using mouse hippocampal slices subjected to Co 2+ [74], an in vitro model of epileptiform-like activity [75]. In this in vitro study, the authors found a two-fold increase in the glycosylated form of Panx1 and no change in Panx2 expression levels within 2 hours after Co 2+ exposure [74].…”

Section: Pannexin1 and Epileptic Seizure Activitysupporting

confidence: 71%

Exciting and not so exciting roles of pannexins

Scemes

Velı́šková

2019

Neuroscience Letters

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It is the current view that purinergic signaling regulates many physiological functions. Pannexin1 (Panx1), a member of the gap junction family of proteins is an ATP releasing channel that plays important physio-pathological roles in various tissues, including the CNS. Upon binding to purinergic receptors expressed in neural cells, ATP triggers cellular responses including increased cell proliferation, cell morphology changes, release of cytokines, and regulation of neuronal excitability via release of glutamate, GABA and ATP itself. Under pathological conditions such as ischemia, trauma, inflammation, epilepsy, extracellular ATP concentrations increases drastically but the consequences of this surge is still difficult to characterize due to its rapid metabolism in ADP and adenosine, the latter having inhibitory action on neuronal activity. For seizures, for instance, the excitatory effect of ATP on neuronal activity is mainly related to its action of P2X receptors, while the inhibitory effects are related to activation of P1, adenosine receptors. Here we provide a mini review on the properties of pannexins with a main focus on Panx1 and its involvement in seizure activity. Although there are only few studies implicating Panx1 in seizures, they are illustrative of the dual role that Panx1 has on neuronal excitability.

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Section: Pannexin1 and Epileptic Seizure Activitysupporting

confidence: 71%

Exciting and not so exciting roles of pannexins

Scemes

Velı́šková

2019

Neuroscience Letters

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“…These events have been referred to as epileptiform burst discharges and have been widely studied to gain insight into the mechanisms underlying epileptiform activity. Historically, CA3 epileptiform burst discharges were produced in tissue removed from normal rodents by electrical stimulation (Stasheff et al 1985), chemoconvulsants such as cobalt, penicillin, kainic acid, tetanus toxin, pilocarpine, bicuculline, and picrotoxin (Dichter & Spencer, 1969; Schwartzkroin & Prince 1977; Wong & Traub, 1983; Fisher & Alger, 1984; Swann & Brady, 1984; Ault et al 1986; Müller & Misgeld, 1991; Nagao et al1996; Rutecki &Yang, 1998; He et al 2009), or perturbation of the neuronal environment by manipulating concentrations of extracellular ions (e.g. Cl - , K + , Mg 2+ , and Ca 2+ ; Schwartzkroin & Prince, 1978; Walther et al 1986; Traynelis & Dingledine, 1988; Perreault & Avoli, 1991; Jensen & Yaari, 1997).…”

Section: Introductionmentioning

confidence: 99%

Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of pilocarpine-treated rats with recurrent seizures

McCloskey

Scharfman

2011

Epilepsy Research

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Rat hippocampal area CA3 pyramidal cells synchronously discharge in rhythmic bursts of action potentials after acute disinhibition or convulsant treatment in vitro. These burst discharges resemble epileptiform activity, and are of interest because they may shed light on mechanisms underlying limbic seizures. However, few studies have examined CA3 burst discharges in an animal model of epilepsy, because a period of prolonged, severe seizures (status epilepticus) is often used to induce the epileptic state, which can lead to extensive neuronal loss in CA3. Therefore, the severity of pilocarpine-induced status epilepticus was decreased with anticonvulsant treatment to reduce damage. Rhythmic burst discharges were recorded in the majority of slices from these animals, between two weeks and nine months after status epilepticus. The incidence and amplitude of bursts progressively increased with time after status, even after spontaneous behavioral seizures had begun. The results suggest that modifying the pilocarpine models of temporal lobe epilepsy to reduce neuronal loss leads to robust network synchronization in area CA3. The finding that these bursts increase long after spontaneous behavioral seizures begin supports previous arguments that temporal lobe epilepsy exhibits progressive pathophysiology.

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“…Recent development in DNA/RNA sequencing technologies simplified study of genetic alterations in MCDs and LNETs on a tissue-wide scale. While some studies concentrated on comparison of tens to hundreds of selected genes from microdessected heterotopic neurons, atypical ganglion cells and astrocytes from FCD and GG 61,62 showing that there was a differential expression in glutamate and GABA receptors, and selected growth factors between the cells in tumor or malformation affected area and cells from control tissues, latter studies used either microarrays or RNA sequencing to interrogate global expression profiles and chromosomal reorganization in LNETs, low grade gliomas and TSC 14,[63][64][65][66][67][68][69][70][71] . Selective sequencing can still be applied to discover mutations in known malformations associated genes 4 .…”

Section: Introductionmentioning

confidence: 99%

“…Those studies concentrated on discovery of additional somatic postzygotic mutations and chromosome reorganization in LNETs and MCDs, while few of them has also reported on increased inflammatory response and activation of complimentary cascade in GG 69 and in TSC 63,68 . Interestingly Stone et al 64 used RNA expression profile and DNA methylation profile in LNETs (GG, DNETs, and with uncertain histologic type) to show that most of those segregate into two distinct groups, one group with astrocytic differentiation and is driven by BRAFV600E mutation and the second group had oligodendroglial differentiation and driven by FGFR1 mutation.…”

Section: Introductionmentioning

confidence: 99%

BRAFV600E Expression in Mouse Neuroglial Progenitors Increase Neuronal Excitability, Cause Appearance of Balloon-like cells, Neuronal Mislocalization, and Inflammatory Immune response

Goz

2019

Preprint

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BACKGROUND: Frequent de-novo somatic mutations in major components (PI3KCA, AKT3, TSC1, TSC2, mTOR, BRAF) of molecular pathways crucial for cell differentiation, proliferation, growth and migration (mTOR, MAPK) has been previously implicated in malformations of cortical development (MCDs) and low-grade neuroepithelial tumors (LNETs) [1][2][3][4][5][6][7] . LNETs are the most frequent tumors found in patients undergoing resective surgery for refractory epilepsy treatment. BRAFV600E is found in up to 70% of LNETs. Previous studies suggest a causal relationship between those de-novo somatic mutations in mTOR, MAPK pathways and seizures occurrence, even without presence of malformation or a tumor 2,3,[8][9][10][11][12][13] In the recently developed mouse models of MCD and GG genetic alterations in MTOR and MAPK components in a small population of cortical cells was enough to disrupt cortical structure, cell morphology and cause seizures. Moreover, administration of MTOR and MAPK specific components inhibitors was enough to decrease seizures and prevent structural malformation. 2,3,9,14,73 . However, the intrinsic electrophysiological mechanisms that may lead to seizures at the single cell level in those studies were not interrogated. This may be due to previous studies on FCD and TSC cases that showed no significant increase in intrinsic excitability of malformed components, including cytomegalic neurons, balloon cells and immature misoriented neurons 51,53,54,[74][75][76][77] .Here we hypothesized that expression of BRAFV600E mutation associated with LNETs alters gene expression in the affected cortical tissue and increase intrinsic neuronal excitability in BRAFV600E neurons, altering passive and active electrophysiological properties. To this end we used In-utero electroporation that allows to introduce genetic manipulation into radial glia progenitor population affecting a small percentage of cells (5-10%) 78, 79 . This manipulation reflects the percentage of mutated alleles found in MCDs 2,4,9,73,80,81 and in GG 14 . Gene expression was examined with RNA sequencing and intrinsic neuronal properties were examined ex-vivo in cortical slices with whole-cell patch clamp. Gene ontology analysis of the tissue-wide expression profiles showed that there was a significant increase in immune response, as well as classic complement pathway activation in BRAFV600E cortical tissue. The decreased biological protein pathways included potassium channels. BRAFV600E expressing neurons had hyperexcitable intrinsic properties most prominent of each was increased action potential firing and low current threshold required to fire action potential (rheobase). Other electrophysiological properties that contribute to hyperexcitability of those neurons include more depolarized resting membrane potential, increased input resistance, lower capacitance, more hyperpolarized action potential voltage threshold. In current-clamp experiments significant SAG and rebound excitation in BRAFV600E neurons were observed, a phenomenon associated with hy...

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Cellular mechanisms of cobalt‐induced hippocampal epileptiform discharges

Cited by 41 publications

References 73 publications

Exciting and not so exciting roles of pannexins

Exciting and not so exciting roles of pannexins

Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of pilocarpine-treated rats with recurrent seizures

BRAFV600E Expression in Mouse Neuroglial Progenitors Increase Neuronal Excitability, Cause Appearance of Balloon-like cells, Neuronal Mislocalization, and Inflammatory Immune response

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