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Kainate Seizures Cause Acute Dendritic Injury and Actin Depolymerization In Vivo
Open accessAbstract
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 calcineurin-dependent regulation of the actin cytoskeleton, suggesting novel therapeutic targets for preventing seizure-induced brain injury.
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“Data from investigators using in vitro ischemia, tissue cooling, and epilepsy support findings that spines can be reversibly altered (Hasbani et al., 2001;Kirov et al., 2004;Zeng et al., 2007).”
From Two-Photon Imaging of Stroke Onset In Vivo Reveals That NMDA-Receptor Independent Ischemic Depolarization Is the Major Cause of Rapid Reversible Damage to Dendrites and Spines (2008) · cites this paper as Zeng et al., 2007
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Metadata
- Authors
- Zeng, L.-H., Xu, L., Rensing, N. R., Sinatra, P. M., Rothman, S. M., & Wong, M.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-10-24
- Volume
- 27
- Issue
- 43
- Pages
- 11604-11613
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3934634
- OpenAlex
- W2081333064
- Cited by
- 158
- References
- 44
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 8 · 2023: 12 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 2 · 2017: 8 · 2016: 13 · 2015: 11 · 2014: 9 · 2013: 10 · 2012: 9
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health (NS057105)
- National Institute of Neurological Disorders and Stroke (R01 NS42936, P30NS057105, NS057105, K02NS045583, R21NS045652, R01NS042936, R01NS056872)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- kainate-induced seizures, secondary generalized seizures, dendritic spines, actin depolymerization, cofilin, calcineurin, actin cytoskeleton, neocortical neurons, seizure-induced brain injury, dendritic morphology, epilepsy
- MeSH terms
- Actins, Animals, Cytoskeleton, Dendrites, Kainic Acid, Mice, Inbred C57BL, Mice, Transgenic, Seizures, Dendritic Spines, Destrin, Mice
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