Regulation of Synaptosomal GLT-1 and GLAST during Epileptogenesis

Peterson, Allison R.; Binder, Devin K.

doi:10.1016/j.neuroscience.2019.05.048

Cited by 26 publications

(22 citation statements)

References 41 publications

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“…Temporal lobe epilepsy (TLE) is the most common form of epilepsy, affecting up to 40 million people worldwide (Hubbard et al, 2016;Peterson and Binder, 2019). TLE is characterized by the occurrence of focal seizures that may impair individuals and is often associated with treatment resistance, where approximately 30% of patients taking antiepileptic drugs present drug resistance that prevents them from living seizure-free (Sarac et al, 2009;Hubbard et al, 2016;Peterson and Binder, 2019).…”

Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

“…Additionally, reactive astrocytes with morphological and functional alterations may be important in epileptogenesis since they contribute to the increase of neuronal excitability. In TLE, this astrocyte-induced excitotoxicity occurs by dysregulation of glutamate astrocytic transporters (EAAT1 or GLAST and EAAT2 or GLT-1), which are responsible for maintaining extracellular glutamate homeostasis (Hubbard et al, 2016;Peterson and Binder, 2019). Different studies have shown that there is a reduction in EAAT1 and EAAT2 expression in the sclerotic hippocampus of TLE patients at RNA or protein levels (Proper et al, 2002;Rakhade and Loeb, 2008).…”

Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

“…Different studies have shown that there is a reduction in EAAT1 and EAAT2 expression in the sclerotic hippocampus of TLE patients at RNA or protein levels (Proper et al, 2002;Rakhade and Loeb, 2008). Furthermore, modifications in GLT-1 function and expression contribute to TLE hyperexcitability and seizure generation (Hubbard et al, 2016;Peterson and Binder, 2019). Different studies have already shown that knockout animal models for GLT-1 exhibit severe spontaneous seizures that can lead to early postnatal death (Tanaka et al, 1997;Hubbard et al, 2016;Peterson and Binder, 2019), and that GLT-1 overexpression may generate pilocarpineinduced epileptogenesis resistant mice (Kong et al, 2012;Sha et al, 2017).…”

Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

“…Furthermore, modifications in GLT-1 function and expression contribute to TLE hyperexcitability and seizure generation (Hubbard et al, 2016;Peterson and Binder, 2019). Different studies have already shown that knockout animal models for GLT-1 exhibit severe spontaneous seizures that can lead to early postnatal death (Tanaka et al, 1997;Hubbard et al, 2016;Peterson and Binder, 2019), and that GLT-1 overexpression may generate pilocarpineinduced epileptogenesis resistant mice (Kong et al, 2012;Sha et al, 2017). In fact, in the intrahippocampal kainic acid mouse model of TLE, a down-regulation of hippocampal astrocytic GLT-1 has been reported, coinciding with the increased excitability (Peterson and Binder, 2019).…”

Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

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Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases

Armada‐Moreira

Gomes

Pina

et al. 2020

Front. Cell. Neurosci.

179

128

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Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes since they can control the levels of glutamate on the synaptic cleft. This control is achieved through glutamate clearance from the synaptic cleft and its underlying recycling through the glutamate-glutamine cycle. The molecular mechanism that triggers excitotoxicity involves alterations in glutamate and calcium metabolism, dysfunction of glutamate transporters, and malfunction of glutamate receptors, particularly N-methyl-D-aspartic acid receptors (NMDAR). On the other hand, excitotoxicity can be regarded as a consequence of other cellular phenomena, such as mitochondrial dysfunction, physical neuronal damage, and oxidative stress. Regardless, it is known that the excessive activation of NMDAR results in the sustained influx of calcium into neurons and leads to several deleterious consequences, including mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, impairment of calcium buffering, the release of pro-apoptotic factors, among others, that inevitably contribute to neuronal loss. A large body of evidence implicates NMDAR-mediated excitotoxicity as a central mechanism in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and epilepsy. In this review article, we explore different causes and consequences of excitotoxicity, discuss the involvement of NMDAR-mediated

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Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

Section: Temporal Side Story: Temporal Lobe Epilepsymentioning

confidence: 99%

See 2 more Smart Citations

Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases

Armada‐Moreira

Gomes

Pina

et al. 2020

Front. Cell. Neurosci.

179

128

View full text Add to dashboard Cite

show abstract

“…20 The above-mentioned results ( Figure 5) have elucidated that the high-regulation of UCA1 could suppress the activation of JAK/STAT signaling induced by KA. Peterson et al 21 have determined that GLAST dysregulation was associated with the development of TLE. Thus, we speculated that UCA1 maybe affect the changes of GLAST expression caused by the occurrence of TLE.…”

Section: Inhibited Glast Expression In Hippocampal Astrocytesmentioning

confidence: 99%

LncRNA‐UCA1 inhibits the astrocyte activation in the temporal lobe epilepsy via regulating the JAK/STAT signaling pathway

Wang

Yao

et al. 2020

J of Cellular Biochemistry

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This article aimed to reveal the mechanism of long noncoding RNA (lncRNA) urothelial cancer‐associated 1 (UCA1) regulated astrocyte activation in temporal lobe epilepsy (TLE) rats via mediating the activation of the JAK/STAT signaling pathway. A model of TLE was established based on rats via kainic acid (KA) injection. All rats were divided into the Sham group (without any treatments), KA group, normal control (NC; injection with empty vector) + KA group, and UCA1 + KA group. The Morris water maze was used to test the learning and memory ability of rats, and the expression of UCA1 in the hippocampus was determined by quantitative real time polymerase chain reaction (qRT‐PCR). Surviving neurons were counted by Nissl staining, and expression levels of glial cells glial fibrillary acidic protein (GFAP), p‐JAK1, and p‐STAT3 and glutamate/aspartate transporter (GLAST) were analyzed by immunofluorescence and Western blot analysis. A rat model of TLE was established by intraperitoneal injection of KA. qRT‐PCR and fluorescence analyses showed that UCA1 inhibited astrocyte activation in the hippocampus of epileptic rats. Meanwhile, the Morris water maze analysis indicated that UCA1 improved the learning and memory in epilepsy rats. Moreover, the Nissl staining showed that UCA1 might have a protective effect on neuronal injury induced by KA injection. Furthermore, the immunofluorescence and Western blot analysis revealed that the overexpression of UCA1 inhibited KA‐induced abnormal elevation of GLAST, astrocyte activation of the JAK/STAT signaling pathway, as well as hippocampus of epilepsy rats. UCA1 inhibited hippocampal astrocyte activation and JAK/STAT/GLAST expression in TLE rats and improved the adverse reactions caused by epilepsy.

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A companion to the preclinical common data elements and case report forms for neuropathology studies in epilepsy research. A report of the TASK3WG2 Neuropathology Working Group of the ILAE/AES Joint Translational Task Force

et al. 2022

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The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force initiated the TASK3 working group to create common data elements (CDEs) for various aspects of preclinical epilepsy research studies, which could help improve the standardization of experimental designs. This article addresses neuropathological changes associated with seizures and epilepsy in rodent models of epilepsy. We discuss CDEs for histopathological parameters for neurodegeneration, changes in astrocyte morphology and function, mechanisms of inflammation, and changes in the blood‐brain barrier and myelin/oligodendrocytes resulting from recurrent seizures in rats and mice. We provide detailed CDE tables and case report forms (CRFs), and with this companion manuscript, we discuss the rationale and methodological aspects of individual neuropathological examinations. The CDEs, CRFs, and companion paper are available to all researchers, and their use will benefit the harmonization and comparability of translational preclinical epilepsy research. The ultimate hope is to facilitate the development of rational therapy concepts for treating epilepsies, seizures, and comorbidities and the development of biomarkers assessing the pathological state of the disease.

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Regulation of Synaptosomal GLT-1 and GLAST during Epileptogenesis

Cited by 26 publications

References 41 publications

Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases

Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases

LncRNA‐UCA1 inhibits the astrocyte activation in the temporal lobe epilepsy via regulating the JAK/STAT signaling pathway

A companion to the preclinical common data elements and case report forms for neuropathology studies in epilepsy research. A report of the TASK3WG2 Neuropathology Working Group of the ILAE/AES Joint Translational Task Force

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