Increased expression of copine VI in patients with refractory epilepsy and a rat model

Zhu, Binglin; Zha, Jing-Si; Long, Yan; Chen, Guojun; Wang, Xuefeng

doi:10.1016/j.jns.2015.11.041

Cited by 15 publications

(12 citation statements)

References 25 publications

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“…Almost two decades later, Zhu et al [331] published the first study focused on the expression of copine 6 in the brain tissue of epileptic patients. Here, they performed quantitative real-time PCR, Western blot and immunofluorescence analysis to evaluate the expression and distribution of this copine in the brain tissue of drug-resistant epileptic patients and pilocarpine-induced epileptic rats.…”

Section: Copine 6 and Epilepsymentioning

confidence: 99%

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Zavala-Tecuapetla

Cuéllar-Herrera

Luna-Munguía

2020

IJMS

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Epilepsy is a chronic brain disease that affects approximately 65 million people worldwide. However, despite the continuous development of antiepileptic drugs, over 30% patients with epilepsy progress to drug-resistant epilepsy. For this reason, it is a high priority objective in preclinical research to find novel therapeutic targets and to develop effective drugs that prevent or reverse the molecular mechanisms underlying epilepsy progression. Among these potential therapeutic targets, we highlight currently available information involving signaling pathways (Wnt/β-catenin, Mammalian Target of Rapamycin (mTOR) signaling and zinc signaling), enzymes (carbonic anhydrase), proteins (erythropoietin, copine 6 and complement system), channels (Transient Receptor Potential Vanilloid Type 1 (TRPV1) channel) and receptors (galanin and melatonin receptors). All of them have demonstrated a certain degree of efficacy not only in controlling seizures but also in displaying neuroprotective activity and in modifying the progression of epilepsy. Although some research with these specific targets has been done in relation with epilepsy, they have not been fully explored as potential therapeutic targets that could help address the unsolved issue of drug-resistant epilepsy and develop new antiseizure therapies for the treatment of epilepsy.

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Section: Copine 6 and Epilepsymentioning

confidence: 99%

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Zavala-Tecuapetla

Cuéllar-Herrera

Luna-Munguía

2020

IJMS

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“…Copine 6 is a member of the copine family, a conserved, C2 domain‐containing, calcium‐dependent, phospholipid‐binding protein group found in diverse eukaryotic organisms . Although previous studies have shown that copine 6 is almost exclusively expressed in the brain, its precise biological function remains unclear . Recently, it has been reported that copine 6 is expressed in the postnatal brain, with peak expression in the hippocampus, and copine 6 knockout mice are deficient in hippocampal long‐term potentiation, learning and memory .…”

Section: Introductionmentioning

confidence: 99%

Impaired learning and memory in rats induced by a high‐fat diet: Involvement with the imbalance of nesfatin‐1 abundance and copine 6 expression

Chen

et al. 2017

J Neuroendocrinology

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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and behaviour was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST) and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin and insulin were measured via enzyme-linked immunosorbent assay, and the protein expressions of p-glycogen synthase kinase-3β (GSK-3β), GSK-3β, p-β-catenin, β-catenin, cyclinD and copine 6 in the hippocampus and prefrontal cortex (PFC) were detected using western blotting. After 4 consecutive weeks of feeding with a high-fat diet, the rats showed obesity; increased plasma concentrations of ALT, glucose, FFA, TC, TG, HDL-C and LDL-C; decreased plasma levels of leptin and insulin; and inflammation and mild hepatocyte steatosis in the liver. Although there was no significant difference between groups with regard to performance in the OFT, EPM or FST, the NAFLD rats showed a decreased sucrose preference index in the SPT and impaired learning and memory in the MWM task. Moreover, the present study provides the first evidence of an increased plasma nesfatin-1 concentration in NAFLD rats, which was significantly correlated with plasma lipid concentrations and behavioural performance. Furthermore, copine 6 and p-β-catenin protein expression decreased and p-GSK-3β increased in the hippocampus and PFC of NAFLD rats. These results suggest that consuming of a high-fat diet for 4 consecutive weeks could successfully induce a NAFLD rat model. More importantly, these results provide the first evidence that impaired learning and memory in NAFLD rats was, at least partly, associated with increased plasma nesfatin-1 concentration and decreased copine 6 expression in the hippocampus and PFC.

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“…For ethical reasons and limitations, we could not obtain normal human brain tissues; thus, we used histologically normal brain tissues obtained from temporal lobectomy performed to treat head trauma2526. Meanwhile, the brain tissue samples of the neocortex with TLE could only be obtained from drug-resistant epileptic patients.…”

Section: Discussionmentioning

confidence: 99%

“…Neocortical tissue samples from twenty-four patients undergoing surgery for medically intractable epilepsy and ten control samples obtained from non-epileptic patients undergoing surgical therapy for post-trauma intracranial hypertension were randomly chosen from the brain tissue bank established in our lab, and the clinical data from the human brain tissue bank have been reported in our previous studies2526. The diagnosis of epilepsy was confirmed in these patients according to criteria established by the International League Against Epilepsy27.…”

Section: Methodsmentioning

confidence: 99%

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NR4A1 Knockdown Suppresses Seizure Activity by Regulating Surface Expression of NR2B

Zhang

Chen

Gao

et al. 2016

Sci Rep

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Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models. Moreover, reciprocal coimmunoprecipitation of NR4A1 and NR2B demonstrated their interaction. Furthermore, the expression of p-NR2B (Tyr1472) in epileptic mice and the expression of NR2B in the postsynaptic density (PSD) were significantly reduced in the lenti-shNR4A1 group, indicating that NR4A1 knockdown partly decreased surface NR2B by promoting NR2B internalization. These results are the first to indicate that the expression of NR4A1 in epileptic brain tissues may provide new insights into the molecular mechanisms underlying epilepsy.

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Increased expression of copine VI in patients with refractory epilepsy and a rat model

Cited by 15 publications

References 25 publications

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Impaired learning and memory in rats induced by a high‐fat diet: Involvement with the imbalance of nesfatin‐1 abundance and copine 6 expression

NR4A1 Knockdown Suppresses Seizure Activity by Regulating Surface Expression of NR2B

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