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

Ouyang, Yanling; Yang, Xiaofeng; Hu, Xiao; Erbayat-Altay, Ebru; Zeng, Ling‐Hui; J, Lee; Wong, Michael

doi:10.1016/j.brainres.2007.01.077

Cited by 19 publications

(15 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 A, B). Compared with saline-injected controls, the decrease in F-actin labeling was seen immediately after termination of the seizures for at least 2 h. Similar to results reported previously (Ouyang et al, , 2007, doublelabeling experiments with MAP2 and PSD95 confirmed the localization of F-actin in dendrites and dendritic spines (data not shown). In a second assay of actin polymerization, insoluble (F-actin) and soluble (G-actin) fractions of actin were measured by Western blotting.…”

Section: Kainate Seizures Cause Acute Activation Of Cofilin and Depolsupporting

confidence: 88%

“…By comparison, pathological neuronal activation, such as with seizures, might disrupt this finely regulated, dynamic system of dendritic actin networks. In support of this idea, we have recently shown that hippocampal seizures induced by 4-AP lead to moderate activation of cofilin, a major actin-depolymerizing factor, and associated depolymerization of F-actin, although these changes were not necessarily associated with any overt structural changes in dendrites, perhaps because of the relatively mild nature of the seizures (Ouyang et al, 2007). In the present study, we demonstrate that kainate seizures cause a stronger activation of cofilin and depolymerization of F-actin, which is associated with dramatic structural changes in dendrites and is, at least in part, mediated by the calcium-activated phosphatase, calcineurin.…”

Section: Discussionmentioning

confidence: 86%

“…The rhodamine-phalloidin labeling method was used, as described previously (Ouyang et al, , 2007, to measure F-actin levels in wild-type C57BL/6 mice after saline or kainate (30 mg/kg, i.p.) injection.…”

Section: Methodsmentioning

confidence: 99%

“…Images of the stratum radiatum of CA1 regions of hippocampus and layer 1-3 of neocortex were acquired with a Zeiss LSM PASCAL confocal microscope. A high-power objective (63ϫ, 1.2 NA) was used to confirm the punctate labeling typical of spines (Ouyang et al, , 2007, and a low-power objective (25ϫ, 0.8 NA) was used to obtain images for regional F-actin intensity measurements. Regions of interest from images were selected within the striatum radiatum of CA1 and layer 1/2 of neocortex to measure the average brightness of F-actin labeling using MetaMorph analysis software.…”

Section: Methodsmentioning

confidence: 99%

“…was injected 2 h before kainate. The neocortex and hippocampi were dissected out and sonicated individually in SDS-PAGE sample buffer containing 3% SDS, 2% ␤-mercaptoethanol, and 5% glycerol in 60 mM Tris buffer, pH 6.7, as described previously (Ouyang et al, , 2007. Samples were boiled for 5 min and stored at Ϫ20°C.…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Kainate Seizures Cause Acute Dendritic Injury and Actin DepolymerizationIn Vivo

Zeng¹,

Xu²,

Rensing³

et al. 2007

J. Neurosci.

149

134

View full text Add to dashboard Cite

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.

show abstract

Section: Kainate Seizures Cause Acute Activation Of Cofilin and Depolsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Kainate Seizures Cause Acute Dendritic Injury and Actin DepolymerizationIn Vivo

Zeng¹,

Xu²,

Rensing³

et al. 2007

J. Neurosci.

149

134

View full text Add to dashboard Cite

show abstract

Expression pattern of Mical‐1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine‐induced rat model

Luo

Zhao

et al. 2011

Synapse

View full text Add to dashboard Cite

Mical-1 is a novel F-actin-disassembly factor that is critical in actin reorganization. It provides a molecular conduit through which actin reorganizes-a hallmark of cell morphological changes, including axon navigation. However, whether Mical-1 is involved in the epileptogenesis remains unknown. Here, we investigate Mical-1 expression pattern in patients with intractable temporal lobe epilepsy (TLE) and pilocarpine-induced rat model. We used double-labeled immunoflurescence, immunohistochemistry, and Western blotting to assess the location and expression of Mical-1 in temporal neocortex of patients with intractable TLE, and the expression pattern of Mical-1 at different time point in the hippocampus and temporal lobe cortex of the pilocarpine-induced rat model. Double-labeled immunofluorescence showed that Mical-1 was coexpressed with neuron-specific enolase (NSE) in the cytoplasm of neurons in temporal neocortex of patients with TLE and hippocampus of rat model. Faint and scattered immunoreactivity for Mical-1 in the neuron of temporal neocortex in TLE group, but strong immunoreactivity for Mical-1 was shown in control subjects. To quantitatively evaluate the Mical-1 immunoreactivity, we measured the mean optical density (OD) of Mical-1. In the hippocampus of pilocarpine-induced rat model, the OD values transient increased at 6 h after seizure then decreased from 1 day to 14 days, and returned to a subnormal level at 60 days. The lowest level of Mical-1 expression occurred at 14 days after seizure in the hippocampus. In the temporal lobe cortex of rat model, the OD values decreased at all time point after kindling compared to the normal group. Furthermore, our Western blot analysis confirmed these expression patterns of Mical-1 from latent stage to chronic stage. Our results indicate that in patients with TLE and pilocarpine-induced rat model, the expression of Mical-1 were followed a downtrend from the latent stage to chronic stage after seizure evoke. Thus, as an effect factor participated in F-actin disassemble, Mical-1 may associate with inner pathophysiological modulation in epilepsy.

show abstract