Pilocarpine-induced status epilepticus increases Homer1a and changes mGluR5 expression

Cavarsan, Clarissa Fantin; Tescarollo, Fabio; Tesone-Coelho, Carolina; Morais, Rafael Leite; Motta, Fabiana Louise; Blanco, Miriam Marcela; Mello, Luiz E.

doi:10.1016/j.eplepsyres.2012.04.011

Cited by 28 publications

(29 citation statements)

References 55 publications

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“…) and chronic electroconvulsive seizures (Altar et al 2004). In the kindling model of epilepsy (Potschka et al 2002), Homer 1a -overexpressing mice show delays in kindling acquisition (Potschka et al 2002), and Homer 1a is up-regulated in response to SE (Cavarsan et al 2012). Homer 1a protein normally contributes to homeostatic scaling (Hu et al 2010), which is likely aberrant in chronic seizures (Frank 2014).…”

Section: Metabotropic Glutamate Receptor Subtypes Regulation and Romentioning

confidence: 99%

Glutamatergic Mechanisms Associated with Seizures and Epilepsy

Barker‐Haliski

White

2015

Cold Spring Harb Perspect Med

314

211

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Epilepsy is broadly characterized by aberrant neuronal excitability. Glutamate is the predominant excitatory neurotransmitter in the adult mammalian brain; thus, much of past epilepsy research has attempted to understand the role of glutamate in seizures and epilepsy. Seizures induce elevations in extracellular glutamate, which then contribute to excitotoxic damage. Chronic seizures can alter neuronal and glial expression of glutamate receptors and uptake transporters, further contributing to epileptogenesis. Evidence points to a shared glutamate pathology for epilepsy and other central nervous system (CNS) disorders, including depression, which is often a comorbidity of epilepsy. Therapies that target glutamatergic neurotransmission are available, but many have met with difficulty because of untoward adverse effects. Better understanding of this system has generated novel therapeutic targets that directly and indirectly modulate glutamatergic signaling. Thus, future efforts to manage the epileptic patient with glutamatergic-centric treatments now hold greater potential.

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Section: Metabotropic Glutamate Receptor Subtypes Regulation and Romentioning

confidence: 99%

Glutamatergic Mechanisms Associated with Seizures and Epilepsy

Barker‐Haliski

White

2015

Cold Spring Harb Perspect Med

314

211

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“…Interestingly, most of the differentially expressed proteins at 1dpi were downregulated in KA-injected mice or expressed only in control animals (NaClinjected mice). Well-known proteins involved in synaptic plasticity, such as Neurabin-2 and Neurochondrin, or involved in neurodegeneration such as Homer1 were downregulated by 0.66, 0.33 and 0.53 fold, respectively [36][37][38] . Additionally, other proteins expressed in neuronal cells were detected only in NaCl-injected animals, such as Ataxin-10, Shank3 and WD repeat-containing protein 47 [39][40][41] .…”

Section: Immediate Protein Expression Response After Se (1dpi)mentioning

confidence: 99%

High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

Bitsika

Duveau²,

Simon-Areces

et al. 2016

J. Proteome Res.

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Uncovering the molecular mechanisms of Mesial temporal lobe epilepsy (MTLE) is critical to identify therapeutic targets. In this study, we performed global protein expression analysis of a kainic acid (KA) MTLE mouse model at various time-points (1d, 3d, 30d post KA injection -dpi), representing specific stages of the syndrome.High resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination to label-free protein quantification, using three processing approaches for quantification, was applied. Following comparison of KA versus NaCl-injected mice, 22, 53 and 175 proteins were differentially (statistically significant) expressed at 1, 3 and 30dpi respectively, according to all 3 quantification approaches. Selected findings were confirmed by multiple reaction monitoring LC-MS/MS. As a positive control, the astrocyte marker GFAP was found to be upregulated (3dpi:1.9 fold; 30dpi:12.5 fold), also verified by IHC. The results collectively suggest that impairment in synaptic transmission occurs even right after initial status epilepticus (1dpi), with neurodegeneration becoming more extensive during epileptogenesis (3dpi) and sustained at the chronic phase (30dpi), where also extensive glial and astrocyte-mediated inflammation is evident. This molecular profile is in line with observed phenotypic changes in human MTLE, providing the basis for future studies on new molecular targets for the disease.

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“…Our group observed an acute increase of c-fos after status epilepticus induction and described that it may also lead to a long-lasting state of c-fos downregulation in the chronic phase (weeks to months) of the pilocarpine model [16]. Investigating some other IEGs after pilocarpine-induced status epilepticus, we found that Homer1a is one of the mRNA proteins that are acutely overexpressed [17]. Medeiros and colleagues found c-fos expression when PTZ and electroshock stimulation are applied together [18].…”

Section: Introductionmentioning

confidence: 89%

“…Thus, Homer1a is an endogenous modulator of an adaptor system which comprises the crosslinking of Homer proteins and their binding partners, among them membrane receptors and channels as well as intracellular pools of releasable calcium [22]. Our previous work showed that during the epileptogenesis process after pilocarpine-induced status epilepticus, the levels of Homer1a increase in the hippocampus and there is a modulation of mGlur5 expression in the entorhinal and piriform cortices [17]. Kirschstein and colleagues showed that after the epileptogenic process induced by pilocarpine, there was a reduction of Homer1a and mGluR5 levels which led to a loss of mGluRdependent long-term depression [27].…”

Section: Introductionmentioning

confidence: 98%