Long-duration epilepsy affects cell morphology and glutamatergic synapses in type IIB focal cortical dysplasia

Adele Finardi, Francesca Colciaghi, Laura Castana, Denise Locatelli, Carlo Efisio Marras, Paola Nobili, Maddalena Fratelli, Manuela Adele Bramerio, Giorgio Lorusso, Giorgio Stefano Battaglia

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

To investigate hypothesized effects of severe epilepsy on malformed cortex, we analyzed surgical samples from eight patients with type IIB focal cortical dysplasia (FCD) in comparison with samples from nine non-dysplastic controls. We investigated, using stereological quantification methods, where appropriate, dysplastic neurons, neuronal density, balloon cells, glia, glutamatergic synaptic input, and the expression of N-methyl-d-aspartate (NMDA) receptor subunits and associated membrane-associated guanylate kinase (MAGUK). In all FCD patients, the dysplastic areas giving rise to epileptic discharges were characterized by larger dysmorphic neurons, reduced neuronal density, and increased glutamatergic inputs, compared to adjacent areas with normal cytology. The duration of epilepsy was found to correlate directly (a) with dysmorphic neuron size, (b) reduced neuronal cell density, and (c) extent of reactive gliosis in epileptogenic/dysplastic areas. Consistent with increased glutamatergic input, western blot revealed that NMDA regulatory subunits and related MAGUK proteins were up-regulated in epileptogenic/dysplastic areas of all FCD patients examined. Taken together, these results support the hypothesis that epilepsy itself alters morphology - and probably also function - in the malformed epileptic brain. They also suggest that glutamate/NMDA/MAGUK dysregulation might be the intracellular trigger that modifies brain morphology and induces cell death.

Original languageEnglish
Pages (from-to)219-235
Number of pages17
JournalActa Neuropathologica
Volume126
Issue number2
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Guanylate Kinases
Malformations of Cortical Development
Synapses
Epilepsy
Neurons
Aspartic Acid
Cell Count
Gliosis
Brain
Neuroglia
Cell Biology
Glutamic Acid
Cell Death
Western Blotting
Proteins

Keywords

  • Dysmorphic neurons
  • Glutamatergic synaptic input
  • MAGUK proteins
  • Malformations of cortical development
  • NMDA receptor
  • Seizure-induced plasticity

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

Cite this

Long-duration epilepsy affects cell morphology and glutamatergic synapses in type IIB focal cortical dysplasia. / Finardi, Adele; Colciaghi, Francesca; Castana, Laura; Locatelli, Denise; Marras, Carlo Efisio; Nobili, Paola; Fratelli, Maddalena; Bramerio, Manuela Adele; Lorusso, Giorgio; Battaglia, Giorgio Stefano.

In: Acta Neuropathologica, Vol. 126, No. 2, 08.2013, p. 219-235.

Research output: Contribution to journalArticle

Finardi, A, Colciaghi, F, Castana, L, Locatelli, D, Marras, CE, Nobili, P, Fratelli, M, Bramerio, MA, Lorusso, G & Battaglia, GS 2013, 'Long-duration epilepsy affects cell morphology and glutamatergic synapses in type IIB focal cortical dysplasia', Acta Neuropathologica, vol. 126, no. 2, pp. 219-235. https://doi.org/10.1007/s00401-013-1143-4
Finardi, Adele ; Colciaghi, Francesca ; Castana, Laura ; Locatelli, Denise ; Marras, Carlo Efisio ; Nobili, Paola ; Fratelli, Maddalena ; Bramerio, Manuela Adele ; Lorusso, Giorgio ; Battaglia, Giorgio Stefano. / Long-duration epilepsy affects cell morphology and glutamatergic synapses in type IIB focal cortical dysplasia. In: Acta Neuropathologica. 2013 ; Vol. 126, No. 2. pp. 219-235.
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