Remodeling dendritic spines in the rat pilocarpine model of temporal lobe epilepsy

Isokawa, Masako

doi:10.1016/s0304-3940(98)00848-9

Cited by 69 publications

(64 citation statements)

References 23 publications

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“…Similar to the clinical findings, a loss of dendritic spines and varicose swelling of dendrites is frequently found in histological sections obtained from rats that had acute seizures or chronic epilepsy induced in vivo by various methods, such as convulsant drugs or electrical kindling [60][61][62][63][64][65], although rarely an increase in dendrites or spines has been reported [66][67][68]. Furthermore, spine loss and other dendritic changes can also occur with in vitro seizure models involving epileptiform bursting in brain slice-cultures [69][70][71][72].…”

Section: Dendritic Abnormalities In Epilepsysupporting

confidence: 64%

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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Section: Dendritic Abnormalities In Epilepsysupporting

confidence: 64%

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

Wong¹

2008

Expert Review of Neurotherapeutics

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“…conventional fixed tissue analysis (Scheibel et al, 1974;Isokawa and Levesque, 1991;Muller et al, 1993;Multani et al, 1994;Drakew et al, 1996;Isokawa, 1998;Jiang et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Dendritic spines represent the structural sites of contact for the majority of excitatory, glutamatergic synaptic inputs onto cortical neurons and are strongly implicated in mechanisms of synaptic plasticity and learning. A variety of studies demonstrate a loss of dendritic spines in pathological specimens from animal seizure models (Olney et al, 1983;Muller et al, 1993;Drakew et al, 1996;Isokawa, 1998;Jiang et al, 1998) or human epilepsy patients (Scheibel et al, 1974;Isokawa and Levesque, 1991;Multani et al, 1994), suggesting that seizures can cause dendritic injury. However, these previous studies using conventional histological analysis of fixed tissue are somewhat limited by the difficulty in distinguishing direct effects of seizures from potential confounding or coincidental factors and by the relatively slow time course of analysis, typically spanning hours to days.…”

Section: Introductionmentioning

confidence: 99%

Kainate Seizures Cause Acute Dendritic Injury and Actin DepolymerizationIn Vivo

Zeng¹,

Xu²,

Rensing³

et al. 2007

J. Neurosci.

149

134

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Seizures may cause brain injury via a variety of mechanisms, potentially contributing to cognitive deficits in epilepsy patients. Although seizures induce neuronal death in some situations, they may also have "nonlethal" pathophysiological effects on neuronal structure and function, such as modifying dendritic morphology. Previous studies involving conventional fixed tissue analysis have demonstrated a chronic loss of dendritic spines after seizures in animal models and human tissue. More recently, in vivo time-lapse imaging methods have been used to monitor acute changes in spines directly during seizures, but documented spine loss only under severe conditions. Here, we examined effects of secondary generalized seizures induced by kainate, on dendritic structure of neocortical neurons using multiphoton imaging in live mice in vivo and investigated molecular mechanisms mediating these structural changes. Higher-stage kainate-induced seizures caused dramatic dendritic beading and loss of spines within minutes, in the absence of neuronal death or changes in systemic oxygenation. Although the dendritic beading improved rapidly after the seizures, the spine loss recovered only partially over a 24 h period. Kainate seizures also resulted in activation of the actin-depolymerizing factor, cofilin, and a corresponding decrease in filamentous actin, indicating that depolymerization of actin may mediate the morphological dendritic changes. Finally, an inhibitor of the calcium-dependent phosphatase, calcineurin, antagonized the effects of seizures on cofilin activation and spine morphology. These dramatic in vivo findings demonstrate that seizures produce acute dendritic injury in neocortical neurons via calcineurindependent regulation of the actin cytoskeleton, suggesting novel therapeutic targets for preventing seizure-induced brain injury.

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“…In patients afflicted with schizophrenia, neuropil degeneration is correlated with an increase in neuronal density and decrease in somatic area (54)(55)(56) and is regulated by apoptotic mechanisms (57). Neuropil degeneration can occur quickly; dendrites of dentate gyrus neurons show signs of degeneration within hours of status epilepticus (58), and deafferentation leads to rapid atrophy of dendritic arbors within hours (59)(60)(61)(62). In hibernating ground squirrels, the dendritic structure and somatic area of neurons in multiple brain areas rapidly regress in response to temperature-induced torpor on the order of hours to days, but there is no evidence that torpor of this form is driven by changes in circulating hormone levels (63).…”

Section: Discussionmentioning

confidence: 99%

Rapid seasonal-like regression of the adult avian song control system

Thompson

Bentley²,

Brenowitz

2007

Proc. Natl. Acad. Sci. U.S.A.

101

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We analyzed how rapidly avian song control nuclei regress after testosterone (T) withdrawal. Regression of neuronal attributes resulting from T withdrawal has been observed in several animal models. The time course over which regression occurs is not known, however. To address this issue, we castrated adult male white-crowned sparrows and rapidly shifted them to short-day photoperiods after being held under breeding conditions (longday photoperiod and systemic T exposure) for 3 weeks. We found that the volume of one song nucleus, HVC, regressed 22% within 12 h after T withdrawal. Changes in HVC neuron density after T withdrawal were dynamic; density increased at 12 h and then decreased by 4 days. HVC neuron number was reduced by 26% by 4 days. The volumes of Area X and the robust nucleus of the arcopallium (RA) were significantly regressed by 7 and 20 days, respectively. RA somatic area and neuronal spacing were significantly reduced by 2 days. The rapidity of HVC regression is unprecedented among vertebrate models of hormone-sensitive neural circuits. These results reveal that the rapid regression of the song control system provides a model for the important role sex steroid hormones play in mediating adult neural plasticity and in neuroprotection.birdsong ͉ neurodegeneration ͉ neuroprotection ͉ plasticity ͉ testosterone

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Remodeling dendritic spines in the rat pilocarpine model of temporal lobe epilepsy

Cited by 69 publications

References 23 publications

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

Kainate Seizures Cause Acute Dendritic Injury and Actin DepolymerizationIn Vivo

Rapid seasonal-like regression of the adult avian song control system

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