Logo image
Anomalous inhibitory circuits in cortical tubers of human tuberous sclerosis complex associated with refractory epilepsy: Aberrant expression of parvalbumin and calbindin-D-28k in dysplastic cortex
Journal article   Peer reviewed

Anomalous inhibitory circuits in cortical tubers of human tuberous sclerosis complex associated with refractory epilepsy: Aberrant expression of parvalbumin and calbindin-D-28k in dysplastic cortex

Ignacio Valencia, Agustin Legido, Karina Yelin, Divya Khurana, Sanjeev V. Kothare and Christos D. Katsetos
Journal of child neurology, v 21(12), pp 1058-1063
01 Dec 2006
PMID: 17156698

Abstract

Clinical Neurology Life Sciences & Biomedicine Neurosciences & Neurology Pediatrics Science & Technology
Damage or loss of inhibitory. cortical gamma-aminobutyric acid (GABA)ergic interneurons is associated with impaired inhibitory control of neocortical pyramidal cells, leading to hyperexcitability and epileptogenesis. The calcium binding proteins parvalbumin and calbindin-D-28k-are expressed in subpopulations of GABAergic local circuit neurons in the neocortex and can serve as neuronotypic markers. Parvalbumin and calbindin-D-28k facilitate the neuron's ability to sustain firing and provide neuroprotection. The goal of this study was to assess the hitherto unknown status of inhibitory interneurons in cortical tubers of human tuberous sclerosis complex. Surgically excised cortical tubers from three patients with tuberous sclerosis complex were evaluated immunohistochemically with antibodies to parvalbumin and calbindin-D28k, Cortical specimens from young patients with intractable seizures, including microdysgenesis (n = 3), postischemic cortical scarring (n = 1), porencephaly (n = 1), postictal gliosis (n = 3), and low-grade neuronal or glial tumors (n = 5), were also examined for comparison. In cortical tubers, calcium binding protein immunoreactivities (calbindin-D-28k > parvalbumin) were present in medium- or large-size dysplastic neurons, whereas giant or ballooned cells were parvalbumin or calbindin-D-28k negative. In microdysgenesis, a nearly normal number of parvalbumin-positive neurons and a decreased number of calbindin-D-28k-positive neurons were present. In peritumoral but more so in gliotic cortex, a coordinate decrease of parvalbumin and calbindin-D28k immunoreactivities was present. Our findings indicate that the expression of parvalbumin or calbindin-D28k by subpopulations of dysplastic neurons in cortical tubers is aberrant and denotes dysfunctional inhibitory circuits inept for excitoprotection.

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Clinical Neurology
Pediatrics
Logo image