Increased levels of acidic calponin during dendritic spine plasticity after pilocarpine‐induced seizures

Ferhat, Lotfi; Esclapez, Monique; Represa, Alfonso; Fattoum, Abdellatif; Shirao, Tomoaki; Ben-Ari, Yehezkel

doi:10.1002/hipo.10136

Cited by 43 publications

(41 citation statements)

References 65 publications

(90 reference statements)

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“…We found that seizure activity causes activation (dephosphorylation) of cofilin and an associated depolymerization of F-actin, even in the absence of major structural changes to the dendrites. While a recent study found that disruption of actin networks may alter seizure threshold (SierraParedes et al, 2006) and other studies indicate that seizures may affect actin-binding proteins (Roth et al, 2001;Ferhat et al, 2003), the present study is among the first to directly show that seizures can modulate actin polymerization, as well as cofilin activation. While it is possible that the actin depolymerization might be a direct pharmacological effect of 4-AP rather than the seizure activity, preliminary data from our and other labs suggest similar effects in other seizure models (Wong, unpublished data), and p-cofilin was decreased bilaterally in this study, despite a unilateral 4-AP injection, consistent with seizure-mediated actions.…”

Section: Discussionmentioning

confidence: 39%

Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes

Ouyang

Yang

et al. 2007

Brain Research

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Seizures may exert pathophysiological effects on dendritic spines, but the molecular mechanisms mediating these effects are poorly understood. Actin represents a major structural protein of dendritic spines, and actin filaments (F-actin) can be depolymerized by the regulatory molecule, cofilin, leading to structural or functional changes in spines in response to normal physiological activity. To investigate mechanisms by which pathophysiological stimuli may affect dendritic spine structure and function, we examined changes in F-actin and cofilin in hippocampus due to 4-aminopyridine (4-AP)-induced seizures/epileptiform activity in vivo and in vitro and investigated possible structural correlates of these changes in actin dynamics. Within an hour of induction, seizure activity caused both a significant decrease in F-actin labeling, indicating depolymerization of F-actin, and a corresponding decrease in phosphorylated cofilin, signifying an increase in cofilin activity. However, 4-AP seizures had no overt short-term structural effects on dendritic spine density. By comparison, high potassium caused a more dramatic decrease in cofilin and an immediate dendritic beading and loss of dendritic spines. These findings indicate that activation of cofilin and depolymerization of Factin represent mechanisms by which seizures may exert pathophysiological modulation of dendritic spines. In addition to affecting non-structural functions of spines, the degree to which overt structural changes occur with actin depolymerization is dependent on the severity and type of the pathophysiological stimulus.

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Section: Discussionmentioning

confidence: 39%

Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes

Ouyang

Yang

et al. 2007

Brain Research

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“…Recent evidence suggests that specific calcium-activated enzymes, such as calcineurin, are activated in animal models of epilepsy [86]. Furthermore, actin and actin-associated proteins are regulated by acute seizures or during chronic epileptogenesis [75,87,88]. In particular, seizures lead to acute depolymerization of filamentous actin, which could directly account for structural changes in dendrites [75].…”

Section: Mechanisms Of Dendritic Injurymentioning

confidence: 99%

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

Wong¹

2008

Expert Review of Neurotherapeutics

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SummaryPeople with epilepsy often experience long-term cognitive dysfunction and other neurological deficits, including memory loss, learning disabilities, and neurobehavioral disorders, which may exhibit a progressive course correlating with worsening seizure control. Furthermore, one-third of epilepsy patients have seizures that are intractable to all available treatments. Thus, novel therapies for seizures and the neurological comorbidities of epilepsy are desperately needed. As most current treatments are merely "symptomatic" therapies that suppress seizures, recently epilepsy researchers have realized the critical need for novel therapeutic strategies targeting the underlying mechanisms of epileptogenesis and seizure-related brain injury. Yet to date, few such "anti-epileptogenic" therapies have emerged or are even in developmental stages. Although many seizure medications modulate the functional or physiological activity of neurons, a relatively unexplored therapeutic strategy for epilepsy are methods for stabilizing the structure of neurons. Human pathological studies and animal models of epilepsy demonstrate obvious structural abnormalities in dendrites of neurons, which could contribute to neuronal dysfunction, epileptogenesis, and cognitive/neurological deficits in epilepsy patients. This dendritic injury may be caused by activity-dependent breakdown of cytoskeletal elements, such as actin. Mechanistically-targeted approaches to limit seizure-related structural changes in dendrites may represent a novel therapeutic strategy for treating epilepsy and its complications.

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“…Actin filament depolymerization by latrunculin A may also alter other NMDA receptor properties, such as protein anchoring to intracellular domains, thus altering the signaling pathways activated by both synaptic and extrasynaptic receptors. [9] Alterations in several actin-related proteins, such as acidic calponin [29] and calpain [30] have been linked to epileptic seizures in different experimental models. We have recently shown that latrunculin A microperfusion has a significant effect on components of the MAPK signaling pathways such as ERK 1/2 and pp38 [27] .…”

Section: Discussionmentioning

confidence: 99%

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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Increased levels of acidic calponin during dendritic spine plasticity after pilocarpine‐induced seizures

Cited by 43 publications

References 65 publications

Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes

Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

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

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