Altered expression of vesicular monoamine transporter 2 in epileptic patients and experimental rats

Jiang, Guohui; Cao, Qingqing; Li, Jie; Zhang, Yujiao; Liu, Xiaoya; Wang, Zhihua; Guo, Fengjin; Chen, Yun; Chen, Yalan; Chen, Guojun; Wang, Xuefeng

doi:10.1002/syn.21663

Cited by 10 publications

(9 citation statements)

References 42 publications

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“…Taking previously mentioned studies into account, it is suggested that the transiently increased VMAT2 might be a compensatory response to enhance monoaminergic neurotransmission to counteract hyperexcitability and epileptic seizures. The decrease in VMAT2 expression after SRS is consistent with the known involvement of monoaminergic alterations in epileptic co-morbidities, such as anxiety and depression, and might contribute to the epilepsy disease progression (Jiang et al, 2013). …”

Section: Slc18 Familysupporting

confidence: 78%

“…Moreover, the expression level of VMAT2 mRNA and protein has been determined in resected neocortices of TLE patients (Jiang et al, 2013) and in the hippocampus and adjacent cortices of rats in different stages of the post-SE pilocarpine model (Jiang et al, 2013). VMAT2 is transiently increased in the acute stage after pilocarpine-induced epileptic seizures, but its expression is clearly decreased after SRS in the hippocampus and temporal lobe cortices of TLE rats.…”

Section: Slc18 Familymentioning

confidence: 99%

“…The conditional VMAT2 −/− results in a depressive-like phenotype and an anxiety-like response (Narboux-Neme et al, 2011). To further investigate whether VMAT inhibition would indeed negatively affect the course of disease progression in epilepsy, these inhibitors could be administrated at different stages of the chronic post-SE pilocarpine model (Jiang et al, 2013). Similarly, it would be most interesting to subject the conditional VMAT2 −/− mice to chronic models of epilepsy.…”

Section: Vmatmentioning

confidence: 99%

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Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Liefferinge¹,

Massie²,

Portelli³

et al. 2013

Front. Cell. Neurosci.

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The vesicular neurotransmitter transporters (VNTs) are small proteins responsible for packing synaptic vesicles with neurotransmitters thereby determining the amount of neurotransmitter released per vesicle through fusion in both neurons and glial cells. Each transporter subtype was classically seen as a specific neuronal marker of the respective nerve cells containing that particular neurotransmitter or structurally related neurotransmitters. More recently, however, it has become apparent that common neurotransmitters can also act as co-transmitters, adding complexity to neurotransmitter release and suggesting intriguing roles for VNTs therein. We will first describe the current knowledge on vesicular glutamate transporters (VGLUT1/2/3), the vesicular excitatory amino acid transporter (VEAT), the vesicular nucleotide transporter (VNUT), vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT) and the vesicular γ-aminobutyric acid (GABA) transporter (VGAT) in the brain. We will focus on evidence regarding transgenic mice with disruptions in VNTs in different models of seizures and epilepsy. We will also describe the known alterations and reorganizations in the expression levels of these VNTs in rodent models for temporal lobe epilepsy (TLE) and in human tissue resected for epilepsy surgery. Finally, we will discuss perspectives on opportunities and challenges for VNTs as targets for possible future epilepsy therapies.

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Section: Slc18 Familysupporting

confidence: 78%

Section: Slc18 Familymentioning

confidence: 99%

Section: Vmatmentioning

confidence: 99%

See 1 more Smart Citation

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Liefferinge¹,

Massie²,

Portelli³

et al. 2013

Front. Cell. Neurosci.

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“…In addition, we identified homozygous loss of function alleles in three genes with proposed roles in synaptic transmission: SLC18A 2, CPLX1 , and SNX14 . Abnormal expression of VMAT2, encoded by SLC18A2, has been proposed to contribute to vulnerability toward epilepsy-related psychiatric disorders and cognitive impairment (Jiang et al, 2013). Our finding complements the single report in the literature of a homozygous missense mutation in this gene and provides our patient possible direct route to treatment with dopamine agonists as described (Rilstone et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease

Karaca

Harel

Pehlivan

et al. 2015

Neuron

263

319

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Development of the human nervous system involves complex interactions between fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families, and homozygous loss of function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations.

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“…Western blot analysis of HIF‐1α immunoreactivity was performed as described previously (Jiang et al, ). Total protein was extracted according to the manufacturer's instructions (Keygen Biotech, Nanjing, China).…”

Section: Methodsmentioning

confidence: 99%

Altered expression of hypoxia‐Inducible factor‐1α participates in the epileptogenesis in animal models

Jiang²,

Chen

et al. 2014

Synapse

Self Cite

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Although epilepsy is a common neurological disorder, its mechanism(s) are still not completely understood. Hypoxia can lead to neuronal cell death and angiogenesis, and the same mechanisms were also found in epilepsy. Hypoxia-inducible factor-1α (HIF-1α) is an important transcription protein that regulates gene expression in the brain and other tissues in response to decreases in oxygen availability. However, little is known regarding the expression of HIF-1α in the epileptic brain and whether HIF-1α interventions affect the epileptic process. The aims of this study are to investigate the expression profile of HIF-1α in rat models and to explore the role of HIF-1α in epilepsy. We performed Western blots and immunofluorescence in a lithium-pilocarpine rat epilepsy model. To determine the role of HIF-1α in epilepsy, we used the HIF-1α agonist DMOG and inhibitor KC7F2 to detect changes in the animal behavior in pentylenetetrazole (PTZ) and lithium-pilocarpine epilepsy models. The expression of HIF-1α was significantly increased after pilocarpine-induced status epilepticus. DMOG significantly prolonged the latent period in the PTZ kindling model and decreased the rate of spontaneous recurrent seizures during the chronic stage in the lithium-pilocarpine model. Conversely, the inhibitor KC7F2 produced an opposite behavioral change. Interestingly, both KC7F2 and DMOG had no effect on the acute stage of pilocarpine model and PTZ convulsive model. Our study suggests that upregulated HIF-1α may be involved in the process of epileptogenesis but not in the acute stage of epilepsy. The modulation of HIF-1α may offer a novel therapeutic target in epilepsy.

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Altered expression of vesicular monoamine transporter 2 in epileptic patients and experimental rats

Cited by 10 publications

References 42 publications

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease

Altered expression of hypoxia‐Inducible factor‐1α participates in the epileptogenesis in animal models

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