Association of Microtubule Dynamics with Chronic Epilepsy

Xu, Xin; Hu, Yun; Xiong, Yan; Li, Zhonggui; Wang, Wei; Du, Chao; Yang, Yong; Zhang, Yanke; Xiao, Fei; Wang, Xuefeng

doi:10.1007/s12035-015-9431-8

Cited by 27 publications

(34 citation statements)

References 31 publications

(44 reference statements)

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“…All temporal neocortical samples were obtained from our human brain bank, as previously described . See supplementary material, Supplementary materials and methods for details.…”

Section: Methodsmentioning

confidence: 99%

“…Samples were obtained from 30 patients [13 males and 17 females; mean age 28.03 ± 12.95 years (range 8–60 years); mean disease course 11.0 ± 4.19 years (range 3–20 years)] who had experienced drug‐resistant complex partial seizures arising from mesial temporal structures. The patients underwent presurgical assessments to determine whether they were appropriate candidates for surgery, as previously described . All samples were collected after a surgical resection.…”

Section: Methodsmentioning

confidence: 99%

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Tubulin β‐III modulates seizure activity in epilepsy

Shangguan

et al. 2017

The Journal of Pathology

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Tubulin -III (TUBB3) is the most dynamic -tubulin isoform expressed in neurons, and is highly expressed in the central nervous system. However, the relationship between TUBB3 and epileptic seizures has not been thoroughly investigated. The aims of this study were to investigate the expression of TUBB3 in patients with temporal lobe epilepsy and two different rat models of chronic epilepsy, and to determine the specific roles of TUBB3 in epilepsy. TUBB3 expression was upregulated in human and rat epileptic tissue. Moreover, TUBB3 expression was associated with inhibitory GABAergic neurons and the inhibitory postsynaptic scaffold protein gephyrin. TUBB3 downregulation attenuated the behavioural phenotypes of epileptic seizures during the pilocarpine-induced chronic phase of epileptic seizures and the pentylenetetrazole kindling process, whereas TUBB3 overexpression had the opposite effect. Whole-cell clamp recordings and western blotting revealed that the amplitude of GABA-A receptor-mediated miniature inhibitory postsynaptic currents and the surface expression of the GABA-A receptor were increased in rats in which TUBB3 expression was downregulated. Importantly, TUBB3 interacted with GABA-A receptor-associated protein, which is known to be involved in GABA-A receptor trafficking. These results indicate that TUBB3 plays a critical role in the regulation of epileptic seizures via GABA-A receptor trafficking, suggesting a molecular mechanism for new therapeutic strategies.

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“…All temporal neocortical samples were obtained from our human brain bank, as previously described . See supplementary material, Supplementary materials and methods for details.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Tubulin β‐III modulates seizure activity in epilepsy

Shangguan

et al. 2017

The Journal of Pathology

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“…The procedure used for intracerebroventricular cannulation and electrode implanting, with minor modifications, was described previously (Logrip et al, 2014; Xu et al, 2015) with minor modifications. Anesthetized rats were fixed in a stereotaxic apparatus (RWD Life Science, Co., Ltd, Shenzhen, China).…”

Section: Methodsmentioning

confidence: 99%

“…Local field potentials (LFPs) were filtered (0.1–1000 Hz), 1000× amplified, and digitized at 4 kHz using an OmniPlex ® D Neural Data Acquisition System (Plexon, Dallas, TX, USA), as described previously (Gong et al, 2009; Xu et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities

Zhang

Gao

Zheng

et al. 2017

Front. Mol. Neurosci.

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Phosphodiesterase regulates the homeostasis of cAMP and cGMP, which increase the strength of excitatory neural circuits and/or decrease inhibitory synaptic plasticity. Abnormally, synchronized synaptic transmission in the brain leads to seizures. A phosphodiesterase 10A (PDE10A) inhibitor PF-2545920 has recently attracted attention as a potential therapy for neurological and psychiatric disorders. We hypothesized that PF-2545920 plays an important role in status epilepticus (SE) and investigated the underlying mechanisms. PDE10A was primarily located in neurons, and PDE10A expression increased significantly in patients with temporal lobe epilepsy. PF-2545920 enhanced the hyperexcitability of pyramidal neurons in rat CA1, as measured by the frequency of action potentials and miniature excitatory post-synaptic current. GluA1 and NR2A expression also increased significantly in post-synaptic densities, with or without SE in rats treated with PF-2545920. The ratio of p-GluA1/GluA1 increased in the presence of PF-2545920 in groups with SE. Our results suggest that PF-2545920 facilitates seizure activity via the intracellular redistribution of GluA1 and NR2A in the hippocampus. The upregulation of p-GluA1 may play an important role in trafficking GluA1 to post-synaptic densities. The data suggest it would be detrimental to use the drug in seizure patients and might cause neuronal hyperexcitability in non-epileptic individuals.

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“…These studies indicate that atlastin‐1 may be essential for neuronal development. It is suggested that the dysregulation of microtubules and vesicle transport facilitates the occurrence and spread of epileptic discharges . Nevertheless, the role of atlastin‐1 in the development of epilepsy is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Atlastin‐1 modulates seizure activity and neuronal excitability

Yang

et al. 2019

CNS Neurosci Ther

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Epilepsy is a neurological disease, and the main clinical manifestation is recurrent seizures. The exact etiology of epilepsy and the pathogenesis of the disorder are not yet fully understood. Atlastin‐1, a dynamin‐like GTPase, interacts with microtubules and is responsible for vesicle formation, both of which are highly associated with the development of epilepsy. Here, we reported that the expression level of atlastin‐1 protein was reduced in the temporal neocortex of patients with temporal lobe epilepsy and in the hippocampus and adjacent cortex of a pentylenetetrazol‐kindled epileptic mouse model. Cells expressing atlastin‐1 coexpressed the inhibitory synaptic marker GAD67 in the temporal cortex and hippocampus of patients with epilepsy and an epileptic mouse model. The lentivirus‐mediated overexpression of atlastin‐1 protein in the hippocampus of mice suppressed seizure activity in behavioral experiments. Patch‐clamp recordings in the Mg2+‐free epilepsy cell model showed that atlastin‐1 overexpression inhibited neuronal excitability by suppressing the discharge frequency of spontaneous action potentials rather than by changing the passive and active properties of action potentials. Inhibitory synaptic transmission, but not excitatory synaptic currents, increased after atlastin‐1 overexpression. These findings suggest that atlastin‐1 likely contributes to the occurrence and development of epilepsy through inhibitory synaptic transmission.

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Association of Microtubule Dynamics with Chronic Epilepsy

Cited by 27 publications

References 31 publications

Tubulin β‐III modulates seizure activity in epilepsy

Tubulin β‐III modulates seizure activity in epilepsy

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities

Atlastin‐1 modulates seizure activity and neuronal excitability

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