Altered axon initial segment in hippocampal newborn neurons, associated with recurrence of temporal lobe epilepsy in rats

Liu, Tiantian; Feng, Li; Liu, Heng‐Fang; Shu, Yi; Xiao, Bo

doi:10.3892/mmr.2017.7017

Cited by 12 publications

(8 citation statements)

References 40 publications

(48 reference statements)

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“…Conversely, hyperactivation of neurons, largely modeled by depolarization of Hc neurons in vitro (Grubb and Burrone, 2010) and in slice cultures (Wefelmeyer et al, 2015), shifts the AIS away from the soma over 48 hours, reducing excitability. Hyperactivation resulting from seizure activity similarly shortens and displaces the AIS in vivo (Liu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Localized Myosin II Activity Regulates Assembly and Plasticity of the Axon Initial Segment

Berger

Leo‐Macias

Yuen

et al. 2018

Neuron

119

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The axon initial segment (AIS) is the site of action potential generation and a locus of activity-dependent homeostatic plasticity. A multimeric complex of sodium channels, linked via a cytoskeletal scaffold of ankyrin G and beta IV spectrin to submembranous actin rings, mediates these functions. The mechanisms that specify the AIS complex to the proximal axon and underlie its plasticity remain poorly understood. Here we show phosphorylated myosin light chain (pMLC), an activator of contractile myosin II, is highly enriched in the assembling and mature AIS, where it associates with actin rings. MLC phosphorylation and myosin II contractile activity are required for AIS assembly, and they regulate the distribution of AIS components along the axon. pMLC is rapidly lost during depolarization, destabilizing actin and thereby providing a mechanism for activity-dependent structural plasticity of the AIS. Together, these results identify pMLC/myosin II activity as a common link between AIS assembly and plasticity.

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Section: Discussionmentioning

confidence: 99%

Localized Myosin II Activity Regulates Assembly and Plasticity of the Axon Initial Segment

Berger

Leo‐Macias

Yuen

et al. 2018

Neuron

119

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“…Doublecortin (DCX) is a protein that is associated with cell migration and differentiation [24, 25]. DCX expression is specific to immature neurons [26, 27]. Thus, the number of DCX-positive cells can reflect the level of neurogenesis [28, 29].…”

Section: Discussionmentioning

confidence: 99%

The Role of Hippocampal Neurogenesis in ANT-DBS for LiCl-Pilocarpine-Induced Epileptic Rats

Tang¹,

He²,

Feng³

et al. 2020

Stereotact Funct Neurosurg

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Purpose: Abnormal neurogenesis in the hippocampus after status epilepticus (SE) has been suggested as a key pathogeny of temporal lobe epilepsy. This study aimed to investigate the effect of deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) on hippocampal neurogenesis in LiCl-pilocarpine-induced epileptic rats and to analyze its relationship with postoperative spontaneous recurrent seizures (SRS) and anxiety. Method: SE was induced by a systemic LiCl-pilocarpine injection in adult male rats. Rats in the DBS group underwent ANT-DBS immediately after successful SE induction. SRS was only recorded during the chronic stage. An elevated plus maze was used to evaluate the level of anxiety in rats 7, 28, and 60 days after SE onset. After the elevated plus-maze experiment, rats were sacrificed under anesthesia in order to evaluate hippocampal neurogenesis. Doublecortin (DCX) was used as a marker for neurogenesis. Results: During the chronic stage, SRS in rats in the DBS group were significantly decreased. The level of anxiety was increased significantly in rats in the DBS group 28 days after SE, while no significant differences in anxiety levels were found 7 and 60 days after SE. The number of DCX-positive cells in the hippocampus was significantly increased 7 days after SE and was significantly decreased 60 days after SE in all rats in which SE was induced. However, the number of DCX-positive cells in the DBS group was significantly lower than that in the other groups 28 days after SE. Conclusions: ANT-DBS may suppress SRS and increase the postoperative anxiety of epileptic rats by influencing hippocampal neurogenesis.

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“…Immunofluorescent labeling was performed based on standard protocols as described previously ( 2 ). The sections were incubated with primary antibodies, including goat doublecortin protein (DCX, 1:125; sc-8066; Santa Cruz Biotechnology, Inc.) and rabbit neuronal nuclei (NeuN, 1:1,000; ab177487; Abcam, Cambridge, MA, USA) at 4°C overnight and visualized with appropriate Alexa Fluor-conjugated secondary antibodies (1:1,000; A32723 and A32732; Invitrogen, Thermo Fisher Scientific, Inc., Waltham, MA, USA) at room temperature for 6 h. All sections were counterstained with 4′,6-diamidino-2-phenylindole (DAPI; Wuhan Boster Biological Technology, Ltd.) and images were captured using a laser scanning confocal microscope (LSM 510; Leica Microsystems GmbH).…”

Section: Methodsmentioning

confidence: 99%

“…Epilepsy is one of the most prevalent chronic neurological disorders, which affects ~65,000,000 individuals worldwide and is a global burden in terms of seizure-related disability, comorbidities and mortality rates ( 1 ). Clinically, temporal lobe epilepsy (TLE) is the most common form of drug-resistant and intractable epilepsy, and is characterized by recurrent spontaneous seizures (SRS) due to neuronal hyperactivity in the brain ( 2 ). Abnormal hippocampal neurogenesis is a prominent feature of TLE, which may contribute to the hippocampal network plasticity associated with epilepsy ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy

Liu

Shu

et al. 2018

Int J Mol Med

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Ephrin-B3 is important in the regulation of cell proliferation, differentiation and migration via cell-cell contact, and can activate the reelin pathway during brain development. However, the effect of ephrin-B3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrin-B3 in pilocarpine-induced status epilepticus (SE) rats was investigated. SYBR Green-based reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrin-B3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis. The data revealed that the mRNA and protein expression levels of ephrin-B3 in the hippocampus decreased during the spontaneous seizure period. Of note, the expression of reelin and its downstream phosphorylation disabled 1 (p-Dab1) were also notably decreased during the spontaneous seizure period, which showed similar dynamic changes as in the expression of ephrin-B3. In addition, it was found that the number of DCX-labeled neuronal progenitor cells was increased in the hippocampus following pilocarpine-induced SE. To further clarify the role of ephrin-B3 in neurogenesis and the reelin pathway in epilepsy, an exogenous ephrin-B3 clustering stimulator, EphB3-Fc, was infused into the bilateral hippocampus of the rats post-SE. Following EphB3-Fc injection, it was found that the expression levels of reelin and p-Dab1 were significantly increased in the epileptic rats following EphB3-Fc injection. The number of DCX-labeled neuronal progenitor cells was reduced in the hippocampus of the epileptic rats. Furthermore, the intensity and frequency of spontaneous recurrent seizures and electroencephalographic seizures were attenuated in the epileptic rats post-injection. These results demonstrated the critical role of ephrin-B3 in regulation of the reelin pathway and hippocampal neurogenesis in epilepsy, providing experimental evidence that ephrin-B3 functions as a potential protective factor in epilepsy, at least in animals.

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Altered axon initial segment in hippocampal newborn neurons, associated with recurrence of temporal lobe epilepsy in rats

Cited by 12 publications

References 40 publications

Localized Myosin II Activity Regulates Assembly and Plasticity of the Axon Initial Segment

Localized Myosin II Activity Regulates Assembly and Plasticity of the Axon Initial Segment

The Role of Hippocampal Neurogenesis in ANT-DBS for LiCl-Pilocarpine-Induced Epileptic Rats

Ephrin‑b3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpine‑induced model of epilepsy

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