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Titolo:
Abnormal morphological and functional organization of the hippocampus in ap35 mutant model of cortical dysplasia associated with spontaneous seizures
Autore:
Wenzel, HJ; Robbins, CA; Tsai, LH; Schwartzkroin, PA;
Indirizzi:
Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 t Neurol Surg, Seattle, WA 98195 USA Univ Washington, Dept Physiol Biophys, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 ysiol Biophys, Seattle, WA 98195 USA Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 rd Hughes Med Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 h Med, Dept Pathol, Boston, MA 02115 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 3, volume: 21, anno: 2001,
pagine: 983 - 998
SICI:
0270-6474(20010201)21:3<983:AMAFOO>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
TEMPORAL-LOBE EPILEPSY; NEURONAL MIGRATION DISORDERS; CYCLIN-DEPENDENT KINASE-5; GRANULE CELL DISPERSION; PRENATAL METHYLAZOXYMETHANOL TREATMENT; UNBIASED STEREOLOGICAL ESTIMATION; KAINATE-TREATED RATS; MOUSE DENTATE GYRUS; CEREBRAL-CORTEX; ANIMAL-MODEL;
Keywords:
epilepsy; dentate gyrus; granule cell dispersion; heterotopia; neuronal migration disorder; biocytin; EEG;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
111
Recensione:
Indirizzi per estratti:
Indirizzo: Schwartzkroin, PA Univ Washington, Dept Neurol Surg, Box 356470, Seattle, WA 98195 USA Univ Washington Box 356470 Seattle WA USA 98195 8195 USA
Citazione:
H.J. Wenzel et al., "Abnormal morphological and functional organization of the hippocampus in ap35 mutant model of cortical dysplasia associated with spontaneous seizures", J NEUROSC, 21(3), 2001, pp. 983-998

Abstract

Cortical dysplasia is a major cause of intractable epilepsy in children. However, the precise mechanisms linking cortical malformations to epileptogenesis remain elusive. The neuronal-specific activator of cyclin-dependent kinase 5, p35, has been recognized as a key factor in proper neuronal migration in the neocortex. Deletion of p35 leads to severe neocortical lamination defects associated with sporadic lethality and seizures. Here we demonstrate that p35-deficient mice also exhibit dysplasia/heterotopia of principalneurons in the hippocampal formation, as well as spontaneous behavioral and electrographic seizures. Morphological analyses using immunocytochemistry, electron microscopy, and intracellular labeling reveal a high degree of abnormality in dentate granule cells, including heterotopic localization of granule cells in the molecular layer and hilus, aberrant dendritic orientation, occurrence of basal dendrites, and abnormal axon origination sites. Dentate granule cells of p35-deficient mice also demonstrate aberrant mossy fiber sprouting. Field potential laminar analysis through the dentate molecular layer reflects the dispersion of granule cells and the structural reorganization of this region. Similar patterns of cortical disorganization havebeen linked to epileptogenesis in animal models of chronic seizures and inhuman temporal lobe epilepsy. The p35-deficient mouse may therefore offer an experimental system in which we can dissect out the key morphological features that are causally related to epileptogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/05/20 alle ore 15:14:11