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 language | English |
|---|---|
| Pages (from-to) | 219-235 |
| Number of pages | 17 |
| Journal | Acta Neuropathologica |
| Volume | 126 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Long-duration epilepsy affects cell morphology and glutamatergic synapses in type IIB focal cortical dysplasia
AU - Finardi, Adele
AU - Colciaghi, Francesca
AU - Castana, Laura
AU - Locatelli, Denise
AU - Marras, Carlo Efisio
AU - Nobili, Paola
AU - Fratelli, Maddalena
AU - Bramerio, Manuela Adele
AU - Lorusso, Giorgio
AU - Battaglia, Giorgio Stefano
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Dysmorphic neurons
KW - Glutamatergic synaptic input
KW - MAGUK proteins
KW - Malformations of cortical development
KW - NMDA receptor
KW - Seizure-induced plasticity
UR - http://www.scopus.com/inward/record.url?scp=84881103293&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881103293&partnerID=8YFLogxK
U2 - 10.1007/s00401-013-1143-4
DO - 10.1007/s00401-013-1143-4
M3 - Article
VL - 126
SP - 219
EP - 235
JO - Acta Neuropathologica
JF - Acta Neuropathologica
SN - 0001-6322
IS - 2
ER -