Analysis of connexin expression during seizures induced by 4-aminopyridine in the rat hippocampus

Medina‐Ceja, Laura; Flores-Ponce, Xóchitl; Santerre, Anne; Morales‐Villagrán, Alberto

doi:10.1186/s12929-015-0176-5

Cited by 17 publications

(15 citation statements)

References 68 publications

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“…Laura et al demonstrated an increase in the protein expression of Cx-32 and Cx-43 in oligodendrocytes in the right dentate gyrus and in principal cells of the hippocampus in 4-aminopyrine –induced seizure within 60 min. 34 In the present study, we demonstrated significant increase in Cx-43 protein in CA3 region of hippocampus in rats treated with PTZ. These results agree with previous studies in which an increase in Cx-43 protein was observed in hippocampal slices treated with pilocarpine and bicuculline.…”

Section: Discussionsupporting

confidence: 62%

Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats

Hussein¹,

Ghalwash²,

Magdy³

et al. 2016

J Epilepsy Res

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Background and Purpose:This study aimed to investigate the effect of ceftriaxone on oxidative stress and gap junction protein (connexin 43, Cx-43) expression in pentylenetetrazole (PTZ) induced kindling model.Methods:Twenty four Sprague dawely rats were divided into 3 equal groups (a) normal group: normal rats. (b) PTZ kindled group: received PTZ at the dose of 50 mg/kg via intraperitoneal injection (i.p.) every other day for 2 weeks (c) ceftriaxone treated group: received ceftriaxone at the dose 200 mg\kg/12 hrs via i.p. injection daily from the 6th dose of PTZ for 3 days. Racine score, latency before beginning the first myoclonic jerk and duration of the jerks used as parameters of behavioral assessment. Immunohistopathological study for Cx-43 expression in hippocampus and measurement of markers of oxidative stress (malondialdehyde [MDA], low reduced glutathione [GSH] and catalase [CAT]) in hippocampal neurons were done.Results:PTZ kindling was associated with behavioral changes (in the form high stage of Racine score, long seizure duration and short latency for the first jerk), enhanced oxidative stress state (as demonstrated by high MDA, low GSH and CAT) and up regulation of Cx43 in hippocampal regions. While, ceftriaxone treatment ameliorated, significantly, PTZ-induced convulsions and caused significant improvement in oxidative stress markers and Cx-43 expression in hippocamal regions (p < 0.05).Conclusions:These findings support the anticonvulsive effects of some beta-lactams antibiotics which could offer a possible contributor in the basic treatment of temporal lobe epilepsy. This effect might be due to reduction of oxidative stress and Cx43 expression.

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Section: Discussionsupporting

confidence: 62%

Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats

Hussein¹,

Ghalwash²,

Magdy³

et al. 2016

J Epilepsy Res

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“…To further understand the relationship between Cx36 and hyperactivity, we asked the reciprocal question: how does hyperactivity affect Cx36? Similar to the seizure susceptibility studies, work to identify this relationship has remained conflicting (Laura et al, 2015;Motaghi et al, 2017;Söhl et al, 2000;X. Wu et al, 2017).…”

Section: Ptz Induced Hyperactivity Causes a Regionally-specific Decrementioning

confidence: 99%

“…Previous findings are also mixed regarding how neuronal hyperactivity affects the expression of Cx36. In rodent seizure models and epilepsy patient post-mortem samples, some groups have found that Cx36 expression was increased (Collignon et al, 2006;Laura, Xóchitl, Anne, & Alberto, 2015;X. Wu, Wang, Hao, & Feng, 2017), while others found decreased Cx36 expression (Condorelli, Trovato-Salinaro, Mudo, Mirone, & Belluardo, 2003;Söhl et al, 2000) or no change (Motaghi, Sayyah, Babapour, & Mahdian, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Wu, Wang, Hao, & Feng, 2017), while others found decreased Cx36 expression (Condorelli, Trovato-Salinaro, Mudo, Mirone, & Belluardo, 2003;Söhl et al, 2000) or no change (Motaghi, Sayyah, Babapour, & Mahdian, 2017). Furthermore, even though seizures result in brain-wide changes in neuronal connectivity (Morgan, Gore, & Abou-Khalil, 2010), seizure-induced changes in Cx36 expression had only been examined in the dorsal telencephalon (cortex and hippocampus) (Condorelli et al, 2003;Laura et al, 2015;Motaghi et al, 2017;X. L. Wu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Effects of constitutive and acute Connexin 36 deficiency on brain-wide susceptibility to PTZ-induced neuronal hyperactivity

Brunal

Clark

et al. 2020

Preprint

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Connexins are transmembrane proteins that form hemichannels allowing the exchange of molecules between the extracellular space and cell interior. Two hemichannels from adjacent cells dock and form a continuous gap junction pore, thereby permitting direct intercellular communication. Connexin 36 (Cx36), expressed primarily in neurons, is involved in the synchronous activity of neurons and may play a role in aberrant synchronous firing, as seen in seizures. To understand the reciprocal interactions between Cx36 and seizure-like neural activity, we examined three questions: a) does Cx36 deficiency affect seizure susceptibility, b) does seizure-like activity affect Cx36 expression patterns, and c) does acute blockade of Cx36 conductance increase seizure susceptibility. We utilize the zebrafish pentylenetetrazol (PTZ; a GABA(A) receptor antagonist) induced seizure model, taking advantage of the compact size and optical translucency of the larval zebrafish brain to assess how PTZ affects brain-wide neuronal activity and Cx36 protein expression. We exposed wild-type and genetic Cx36-deficient (cx35.5- /-) zebrafish larvae to PTZ and subsequently mapped neuronal activity across the whole brain, using phosphorylated extracellular-signal-regulated kinase (pERK) as a proxy for neuronal activity. We found that cx35.5-/- fish exhibited region-specific susceptibility and resistance to PTZ-induced hyperactivity compared to wild-type controls, suggesting that genetic Cx36 deficiency may affect seizure susceptibility in a region-specific manner. Regions that showed increased PTZ sensitivity include the dorsal telencephalon, which is implicated in human epilepsy, and the lateral hypothalamus, which has been underexplored. We also found that PTZ-induced neuronal hyperactivity resulted in a rapid reduction of Cx36 protein levels. 30 minutes and one-hour exposure to 20 mM PTZ significantly reduced the expression of Cx36. This Cx36 reduction persists after one-hour of recovery but recovered after 3-6 hours. This acute downregulation of Cx36 by PTZ is likely maladaptive, as acute pharmacological blockade of Cx36 by mefloquine results in increased susceptibility to PTZ-induced neuronal hyperactivity. Together, these results demonstrate a reciprocal relationship between Cx36 and seizure-associated neuronal hyperactivity: Cx36 deficiency contributes region-specific susceptibility to neuronal hyperactivity, while neuronal hyperactivity-induced downregulation of Cx36 may increase the risk of future epileptic events.

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“…The index of the opening of Kv1.4 channel is the decrease in the ratio of the final/ peak, which indicates more inactivation, while the increase in the ratio showed the block of the Kv1.4 channel showing less inactivation. We hypothesise that the enhancement of the Kv1.4 channel expressed in oocytes is a model to treat epilepsy; its main blocker, 4-AP, is a drug to induce epilepsy (44).…”

Section: Purification Of the Biocompoundsmentioning

confidence: 99%

The Effects of 4-Hydroxybenzoic Acid Identified from Bamboo (Dendrocalamus asper) Shoots on Kv1.4 Channel

Zhang

Mohamad

Wong

et al. 2018

MJMS

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Background: Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating Shaker-related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K + across the cellular membrane. Methods: Chemical compounds from Dendrocalamus asper bamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted from Xenopus laevis. The current were detected by the two-microelectrode voltage clamp, holding potential starting from −80 mV with 20 mV stepup until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels with n ≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 µM, 10 µM, 100 µM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control. 4-hydroxybenzoic acid (4-hba) is a nonflavonoid phenolic compound from benzoic acid derivatives (BADs) along with other biocompounds such as salicylic acid, gallic acid and vanilic acid (18). It constitutes of aromatic benzene ring, hydroxyl substituent and functional derivative that influences the mechanisms, biological activities and properties (19). It is able to pass through blood vessels, blood brain barriers (BBB) and cerebrospinal fluid (CSF) due to its low molecular weight (138.12074 Da) (20). As to date, there are not many toxicity studies of this compound on human however, it has been recorded to be slightly irritating to skin and eyes and the maximum bodily intake is estimated to be 0.067 mg/kg/day (for body weight; 70 kg) (21). Other than being used in pharmaceuticals and cosmetic products, 4-hba has been reported to have antifungal, antialgal, antimutagenic, antisickling properties, extrogenic activity and used as trapping agent on hydroxyl radical generation using cerebral ischemia and reperfusion (22).Voltage-gated potassium channels play essential role in restoring the membrane potential and signaling subsequent action potential during neuronal regulation. It is the most abundant and diverse ionic channel identified in the human body with more than 40 types encoded by more than 70 genes and classified into 12 subfamilies (Kv1-Kv12) (23). Kv1 family (Shaker) is mostly distributed around b...

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Analysis of connexin expression during seizures induced by 4-aminopyridine in the rat hippocampus

Cited by 17 publications

References 68 publications

Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats

Beta Lactams Antibiotic Ceftriaxone Modulates Seizures, Oxidative Stress and Connexin 43 Expression in Hippocampus of Pentylenetetrazole Kindled Rats

Effects of constitutive and acute Connexin 36 deficiency on brain-wide susceptibility to PTZ-induced neuronal hyperactivity

The Effects of 4-Hydroxybenzoic Acid Identified from Bamboo (Dendrocalamus asper) Shoots on Kv1.4 Channel

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