LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization
Grote A, Robens BK, Blümcke I, Becker AJ, Schoch S, Gembe E (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 86
Pages Range: 170-6
DOI: 10.1016/j.nbd.2015.11.021
Abstract
Correct positioning and differentiation of neurons during brain development is a key precondition for proper function. Focal cortical dysplasias (FCDs) are increasingly recognized as causes of therapy refractory epilepsies. Neuropathological analyses of respective surgical specimens from neurosurgery for seizure control often reveal aberrant cortical architecture and/or aberrantly shaped neurons in FCDs. However, the molecular pathogenesis particularly of FCDs with aberrant lamination (so-called FCD type I) is largely unresolved. Lipoproteins and particularly low-density lipoprotein receptor-related protein 12 (LRP12) are involved in brain development. Here, we have examined a potential role of LRP12 in the pathogenesis of FCDs. In vitro knockdown of LRP12 in primary neurons results in impaired neuronal arborization. In vivo ablation of LRP12 by intraventricularly in utero electroporated shRNAs elicits cortical maldevelopment, i.e. aberrant lamination by malpositioning of upper cortical layer neurons. Subsequent epilepsy phenotyping revealed pentylenetetrazol (PTZ)-induced seizures to be aggravated in cortical LRP12-silenced mice. Our data demonstrates IUE mediated cortical gene silencing as an excellent approach to study the role of distinct molecules for epilepsy associated focal brain lesions and suggests LRP12 and lipoprotein homeostasis as potential molecular target structures for the emergence of epilepsy-associated FCDs.
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APA:
Grote, A., Robens, B.K., Blümcke, I., Becker, A.J., Schoch, S., & Gembe, E. (2016). LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization. Neurobiology of Disease, 86, 170-6. https://doi.org/10.1016/j.nbd.2015.11.021
MLA:
Grote, Alexander, et al. "LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization." Neurobiology of Disease 86 (2016): 170-6.
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