The effects of salmon calcitonin on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole-induced epilepsy model in rats

Taşkıran, Ahmet Şevki; Özdemir, Ercan; Gümüş, Erkan; Ergül, Mustafa

doi:10.1016/j.yebeh.2020.107501

Cited by 24 publications

(16 citation statements)

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“…In our study, PTZ kindling procedure triggered the inflammatory process in the brain which was manifested by up-regulation of TNF-α, IL-1β, and IL-6 mRNA levels in the prefrontal cortex and/or hippocampus of mice. These findings are consistent with previous results (Gao et al 2018;Singh et al 2019;Taskıran et al 2020). The only statistically significant change of the pro-inflammatory markers in the VPA-and pterostilbene-treated PTZ-kindled mice was the reduction of TNF-α mRNA expression in the hippocampus.…”

Section: Discussionsupporting

confidence: 93%

“…We noted that the PTZ-induced kindling procedure down-regulated GABA level in the prefrontal cortex and hippocampus but did not cause any statistically significant changes of glutamate concentration in these brain structures. Altered levels of neurotransmitters, i.e., a decrease of GABA and an increase of glutamate concentrations, in brains of PTZ-kindled rodents have been reported in numerous studies; however, these parameters were most often evaluated in the whole brain (Koshal and Kumar 2016;Kumar and Kumar 2017;Kumar et al 2016;Taskıran et al 2020). If the levels of neurotransmitters were evaluated in the individual brain structures, the changes were variable (Alachkar et al 2020a;Sejima et al 1997;Singh et al 2013).…”

Section: Discussionmentioning

confidence: 99%

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Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

et al. 2021

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Rationale Pterostilbene is the 3,5-dimethoxy derivative of resveratrol with numerous beneficial effects including neuroprotective properties. Experimental studies revealed its anticonvulsant action in the acute seizure tests. Objectives The purpose of the present study was to evaluate the effect of pterostilbene in the pentetrazol (PTZ)–induced kindling model of epilepsy in mice as well as to assess some possible mechanisms of its anticonvulsant action in this model. Methods Mice were repeatedly treated with pterostilbene (50–200 mg/kg) and its effect on the development of seizure activity in the PTZ kindling was estimated. Influence of pterostilbene on the locomotor activity and anxiety- and depression-like behavior in the PTZ-kindled mice was also assessed. To understand the possible mechanisms of anticonvulsant activity of pterostilbene, γ-aminobutyric acid (GABA) and glutamate concentrations in the prefrontal cortex and hippocampus of the PTZ-kindled mice were measured using LC–MS/MS method. Moreover, mRNA expression of BDNF, TNF-α, IL-1β, IL-6, GABRA1A, and GRIN2B was determined by RT-qPCR technique. Results We found that pterostilbene at a dose of 200 mg/kg considerably reduced seizure activity but did not influence the locomotor activity and depression- and anxiety-like behavior in the PTZ-kindled mice. In the prefrontal cortex and hippocampus, pterostilbene reversed the kindling-induced decrease of GABA concentration. Neither in the prefrontal cortex nor hippocampus pterostilbene affected mRNA expression of IL-1β, IL-6, GABRA1A, and GRIN2B augmented by PTZ kindling. Pterostilbene at a dose of 100 mg/kg significantly decreased BDNF and TNF-α mRNA expression in the hippocampus of the PTZ-kindled mice. Conclusions Although further studies are necessary to understand the mechanism of anticonvulsant properties of pterostilbene, our findings suggest that it might be considered a candidate for a new antiseizure drug.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

et al. 2021

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“…It has been shown that glutamate-induced cytotoxicity increases proin ammatory cytokines, which are associated with nervous system disorders (Chaparro-Huerta et al 2005). The previous ndings have found that sCT has an antiin ammatory effect by inhibiting proin ammatory cytokines production in the brain and blood tissues (Zhang et al 2017;Taskıran et al 2020). Furthermore, it has been claimed that other types of calcitonin, such as human calcitonin, decreases IL-1 stimulated chondrocytes activation by suppressing the p50-NF-κB pathway (Bai et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, some studies have reported that different types of calcitonin have positive effects on the central nervous system. Furthermore, evidence has been suggested that sCT is closely related to the glutamatergic system, such as the NMDA and AMPA receptors, and glutamate releasing (Kilinc et al 2018;Taskıran et al 2020). However, its effect on glutamate-induced cytotoxicity and underlying mechanisms are still unclear.…”

Section: Introductionmentioning

confidence: 99%

The effect of salmon calcitonin against glutamate-induced cytotoxicity in the C6 cell line and the roles the inflammatory and nitric oxide pathways play

Taşkıran

Ergül

2021

Metab Brain Dis

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Recent evidence has shown that salmon calcitonin (sCT) has positive effects on the nervous system.However, its effect and mechanisms on glutamate-induced cytotoxicity are still unclear. The current experiment was designed to examine the effect of sCT on glutamate-induced cytotoxicity in C6 cells, involving the in ammatory and nitric oxide stress pathways. The study used the C6 glioma cell line. Four cell groups were prepared to evaluate the effect of sCT on glutamate-induced cytotoxicity. The control group was without any treatment. Cells in the glutamate group were treated with 10 mM glutamate for 24 h. Cells in the sCT group were treated with various concentrations (3, 6, 12, 25, and 50 µg/mL) of sCT for 24 hours. Cells in the sCT + glutamate group were pre-treated with various concentrations of sCT for 1 hour and then exposed to glutamate for 24 hours. The cell viability was evaluated with an XTT assay. Nuclear factor kappa b (NF-kB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), caspase-3, and caspase-9 levels in the cells were measured by ELISA kits. Apoptosis was detected by ow cytometry method. sCT at all concentrations signi cantly improved the cell viability in C6 cells after glutamateinduced cytotoxicity (p < 0.001). Moreover, sCT signi cantly reduced the levels of NF-kB (p < 0.001), TNFα, and IL-6 levels (p < 0.001). sCT also decreased nNOS, NO, and cGMP levels (P < 0.001). Furthermore, it decreased the apoptosis rate and increased the live-cell rate in the ow cytometry (P < 0.001). In conclusion, sCT has protective effects on glutamate-induced cytotoxicity in C6 glial cells by inhibiting in ammatory and nitric oxide pathways. sCT could be a useful supportive agent for people with neurodegenerative symptoms.

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“…Epilepsy can cause the activation and proliferation of microglia and astrocytes, which are involved in various pathological processes such as in ammation and apoptosis in central system diseases [32,33] . At the same time, epileptic seizures will increase oxidative stress and promote the production of reactive oxygen species, leading to excessive neuronal excitement, oxidative damage, cells apoptosis and long-term intracranial biochemical changes [34,35] . Therefore, it is believed that the in ammatory and oxidative stress responses are the underlying mechanisms of epilepsy neuropathology.…”

Section: Discussionmentioning

confidence: 99%

Genistein Protects Epilepsy-Induced Brain Injury Through Regulating The JAK2/STAT3 and Keap1/Nrf2 Signaling Pathways in The Developing Rats

Huang

Feng

et al. 2021

Preprint

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Background: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons that lead to brain dysfunction. Recurrent seizures or status epilepticus can cause irreversible brain damage. The JAK2-STAT3 signal transduction pathway is stimulated by cytokines and involved in various pathological processes including inflammation, apoptosis and immune regulation in central system diseases. Keap1/Nrf2 is an important anti-oxidative stress pathway, which can reduce the toxic effects of oxygen free radicals and endogenous toxins on neurons. Genistein (Gen) can modulate inflammation and neuronal apoptosis, and may thereby have antiepileptic effects. This study aimed to explore the regulation of Genistein on JAK2/STAT3 and Keap1/Nrf2 signaling pathway and the protective effects on brain injury after epilepsy. Methods: Pentylenetetrazole (PTZ) was used to induce epilepsy in developing rats and Genistein was used for pretreatment of epilepsy. The seizure latency, grade scores and duration of the first generalized tonic-clonic seizure (GTCs) were recorded. Hippocampus tissue was sampled at 24 hours post-epilepsy. Immunofluorescence staining was used to observe the number of mature neurons, activated microglia and astrocytes in the hippocampal CA1 region. Western blot and qRT-PCR were used to determine the protein and mRNA levels of p-JAK2, p-STAT3, TNF-α, IL-1β, Keap1, Nrf2, HO-1, NQO1, caspase3, Bax and Bcl2 in the hippocampus. Results: Immunofluorescence showed that the number of neurons significantly decreased, and activated microglia and astrocytes significantly increased after epilepsy; Western blot and q-PCR showed that the expressions of p-JAK2, p-STAT3, TNF-α, IL-1β, Keap1, caspase3 and Bax significantly increased, while Nrf2, HO-1, NQO1 and Bcl-2 were significantly reduced after epilepsy. These effects were reversed by Genistein treatment. Moreover, Genistein was found to prolong seizure latency and reduce seizure intensity score and duration of generalized tonic-clonic seizures(GTCs). Conclusions: Genistein can activate the Keap1/Nrf2 antioxidant stress pathway and attenuate the activation of microglia and astrocytes. Genistein also inhibits the JAK2-STAT3 inflammation pathway and expression of apoptotic proteins, and increases the number of surviving neurons, thus having a protective effect on epilepsy-induced brain damage.

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The effects of salmon calcitonin on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole-induced epilepsy model in rats

Cited by 24 publications

References 44 publications

Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

Anticonvulsant effect of pterostilbene and its influence on the anxiety- and depression-like behavior in the pentetrazol-kindled mice: behavioral, biochemical, and molecular studies

The effect of salmon calcitonin against glutamate-induced cytotoxicity in the C6 cell line and the roles the inflammatory and nitric oxide pathways play

Genistein Protects Epilepsy-Induced Brain Injury Through Regulating The JAK2/STAT3 and Keap1/Nrf2 Signaling Pathways in The Developing Rats

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