Changes in extracellular amino acid concentrations in the rat hippocampus after in vivo actin depolymerization with latrunculin A

Oreiro-García, Mª Teresa; Vázquez-Illanes, M D; Sierra-Paredes, Germán; Sierra‐Marcuño, German

doi:10.1016/j.neuint.2007.01.005

Cited by 12 publications

(9 citation statements)

References 41 publications

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“…Thus, Latrunculin A microperfusion in rat hippocampus stands as a potential model to study the epileptogenic process in the adult animal . On this regard, rats treated with intrahippocampal Latrunculin A show a permanent decrease of picrotoxin seizure threshold , alterations in extracellular amino acid concentrations (Oreiro-García et al 2007), and also an increased sensitivity to the epileptogenic action of high concentrations of glutamate and glycine (Vazquez-Lopez et al 2006). Recently, we aimed to determine how in vivo F-actin disruption in rats affects AMPA and NMDA receptors subunit composition and traffic, and how these changes affect plasticity-related intracellular signaling in rat hippocampus synapses in both proposed animal models for acute and chronic epileptogenesis processes (Freire-Cobo et al 2014).…”

Section: Introductionmentioning

confidence: 99%

The Calcineurin Inhibitor Ascomicin Interferes with the Early Stage of the Epileptogenic Process Induced by Latrunculin A Microperfusion in Rat Hippocampus

Freire-Cobo

Sierra-Paredes

Freire

et al. 2014

J Neuroimmune Pharmacol

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Latrunculin A microperfusion in rat hippocampus has shown to be an effective model of acute and chronic seizures for neurochemical studies. The intervention over early synaptic plasticity changes after the epileptogenesis onset represents a big challenge on the design of a suitable therapy to impair the epilepsy development. We previously suggested that receptor location might be essential for controlling neuronal excitability, and that disruption of local cytoskeletal dynamics followed by drastic changes in the synaptic/extrasynaptic ratio of NMDA, AMPA receptors and their subsequent downstream signalling may play an important role in the pathogenesis of seizures. In the present study, we performed a pharmacological intervention in the Latrunculin model by using Ascomicin (ASC) and Phenytoin (PHT). We pointed out the inhibitory action of ASC over the protein phosphatase 2B (PP2B). PP2B pathological mechanism involves changes in actin cytoskeleton and showed to avoid those subsequent changes previously observed in PSD components. On the contrary, PHT didn't seem to modify the F-actin depolymerization process induced, showing a similar redistribution pattern from the PSD towards the extrasynaptic site of several molecular components with more or less dependence on actin for their location, including glutamate receptors. Overall, we propose that the early intervention over changes on the synapse during the epileptogenic process might represent the best approach to avoid the onset of chronic refractory seizures our model. On this regard, the therapeutic potential of ASC, FK506 and derivatives should be further explored as a possible tool in the intervention over epilepsy and other brain diseases.

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Section: Introductionmentioning

confidence: 99%

The Calcineurin Inhibitor Ascomicin Interferes with the Early Stage of the Epileptogenic Process Induced by Latrunculin A Microperfusion in Rat Hippocampus

Freire-Cobo

Sierra-Paredes

Freire

et al. 2014

J Neuroimmune Pharmacol

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“…However, the need for new experimental models of chronic epilepsy, and for integrating existing models into the process of therapy discovery has been repeatedly pointed out [25,26] . Latrunculin A microperfusion in the rat hippocampus has shown to be an effective model of acute and chronic seizures both for neurochemical studies [17] and for testing novel anticonvulsant drugs [21] . Moreover, latrunculin A microperfusion may be a useful alternative model for studying epileptogenic processes, as seizures are not the consequence of a previous status epilepticus.…”

Section: Discussionmentioning

confidence: 99%

“…Microdialysis methods have been described elsewhere in detail [17,21] . Adult male Swiss mice, weighing 35-40 g were used.…”

Section: Methodsmentioning

confidence: 99%

“…Interactions between the intracellular domains of NMDA receptors, several cytoskeletal elements and submembrane proteins of the postsynaptic density are essential for receptor location dynamics. [11] The actin cytoskeleton is also likely to play a role in the regulation of amino acid neurotransmitter extracellular concentrations by modifying uptake and release by both neurons and glia [15,16,17] . The synaptic vesicle cycle appears to be influenced by the actin cytoskeleton, [15] which also regulates the availability of the reserve synaptic vesicle pool, affects synapstic vesicle exocytosis and it's required for clathrin-mediated endocytosis [18] .…”

Section: Research Highlightmentioning

confidence: 99%

“…The rats treated with intrahippocampal latrunculin A show also a long-term decrease of picrotoxin seizure threshold [8] , several changes in extracellular amino acid neurotransmitter concentrations, [17] and they are highly susceptible to the epileptogenic action of increased concentrations of glutamate and glycine. [20] Latrunculin A-induced seizures, as well as neurochemical changes associated to them can be prevented by antiepileptic drugs.…”

Section: Research Highlightmentioning

confidence: 99%

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Partial seizures induced by latrunculin A microperfusion in the mouse hippocampus: Role of extracellular glutamate and NMDA receptors

Alonso-Alonso¹,

Freire-Cobo²,

Vázquez-Illanes³

et al. 2015

Mol Cell Epilepsy

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We have previously reported that in vivo de-polymerization of F-actin filaments induces acute and chronic seizures in mice and rats. On these basis, we have investigated the effect of latrunculin A microdialysis in the mice hippocampus on seizure patterns, F-actin filaments and NMDA receptors. Latrunculin A (8 g/ml) was perfused for three consecutive days into the mice hippocampus using microdialysis probes with continuous EEG and video monitoring. After microdialysis experiments, F-actin depolymerization and synaptic and extrasynaptic NR1 protein levels were investigated. Intrahippocampal latrunculin A microperfusion induced partial seizures during the third day of perfusion, and the animals started showing spontaneous partial seizures one month after treatment. Increased levels of extracellular glutamate via microdialysis probes induced seizures in pre-treated mice. F-actin levels were significantly decreased, while NMDA receptor density increased both in synaptic and non-synaptic locations. These results support the hypothesis that actin disruption might be not just a consequence but also a possible cause of epileptic seizures. Actin depolymerization-induced seizures are related to an increase in synaptic and extrasynaptic NMDA receptors and to changes in the extracellular environment. We propose a new experimental model of epilepsy in mice which has been shown to be useful in the study of the biochemical changes that may lead to chronic seizures, and a new method for testing the efficacy of novel antiepileptic drugs in chronic animals.

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Microdialysis as a Tool to Unravel Neurobiological Mechanisms of Seizures and Antiepileptic Drug Action

Smolders

Clinckers

Michotte

2011

Applications of Microdialysis in Pharmaceutical Science

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Changes in extracellular amino acid concentrations in the rat hippocampus after in vivo actin depolymerization with latrunculin A

Cited by 12 publications

References 41 publications

The Calcineurin Inhibitor Ascomicin Interferes with the Early Stage of the Epileptogenic Process Induced by Latrunculin A Microperfusion in Rat Hippocampus

The Calcineurin Inhibitor Ascomicin Interferes with the Early Stage of the Epileptogenic Process Induced by Latrunculin A Microperfusion in Rat Hippocampus

Partial seizures induced by latrunculin A microperfusion in the mouse hippocampus: Role of extracellular glutamate and NMDA receptors

Microdialysis as a Tool to Unravel Neurobiological Mechanisms of Seizures and Antiepileptic Drug Action

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