Abstracts

Inhibitory Circuits in Epilepsy-Associated Gangliogliomas and in the Perilesional Epileptic Cortex

Abstract number : 4.002
Submission category : Translational Research-Human Tissue & Pathology
Year : 2006
Submission ID : 6911
Source : www.aesnet.org
Presentation date : 12/1/2006 12:00:00 AM
Published date : Nov 30, 2006, 06:00 AM

Authors :
1Karin Boer, 1Sandra Redeker, 2Wim G.M. Spliet, 3Peter C. van Rijen, 1Dirk Troost, and 1Eleonora Aronica

Developmental glioneuronal lesions, such as gangliogliomas (GG) are increasingly recognized causes of chronic pharmaco-resistant epilepsy. The cellular mechanism(s) underlying the epileptogenicity of GG remain largely unknown. It has been postulated that chronic epilepsy in patients with malformations of cortical development is associated with dysfunction of the inhibitory GABAergic system. We aimed to identify the subtypes of interneurons present within GG specimens and the expression and cellular distribution patterns of GABA[sub] [/sub]receptors (GABAR) and GABA transporter 1 (GAT1). The expression of the various components of the GABAergic system were also analysed in the perilesional cortex., We investigated immunocytochemically the expression of parvalbumin, calbindin, calretinin, neuropeptide Y (NPY), GABA[sub]A[/sub]R (a1 subunit), GABA[sub]B[/sub] (R1 and R2) and GAT-1 in 30 specimens of GG obtained during epilepsy surgery, including 10 cases with sufficient amount of both perilesional and adjacent normal control cortex., Immunocytochemistry for parvalbumin, calbindin, calretinin, neuropeptide Y demonstrate the presence of inhibitory neurons of different subtypes within the GG specimens. Most interneurons were NPY positive, whereas fewer reacted to calretinin, calbindin and parvalbumin. Both GABA[sub]A[/sub]R and GABA[sub]B[/sub]R (R1 and R2) subtypes were detected within the neuronal component of GG specimens. In addition, GABA[sub]B[/sub]R2 immunoreactivity (IR) was observed in glial cells. GG specimens displayed also expression of GAT-1 IR. Compared to normal cortex, reduced perilesional IR for parvalbumin was observed in 70 %, for calbindin in 60 % and for GABAR and GAT-1 in 30 % of the specimens. Increased staining was detected for NPY in 80 % of the cases., The cellular distribution of components of the GABAergic system in GG, together with the perilesional changes suggest that alterations of the GABAergic system may contribute to the complex abnormal functional network of these highly epileptogenic developmental lesions., (Supported by National Epilepsy Fund - [ldquo]Power of the Small[rdquo]/ Hersenstichting Nederland (NEF 02-10; NEF 05-11, E. Aronica and K. Boer) and by the Epilepsy Institute of the Netherlands (Heemstede, The Netherlands; E. Aronica).)
Translational Research