Developmental glioneuronal lesions, such as
gangliogliomas (GG) are increasingly recognized causes of chronic pharmaco-resistant
epilepsy. It has been postulated that chronic
epilepsy in patients with
malformations of cortical development is associated with dysfunction of the inhibitory
GABA-ergic system. We aimed to identify the subtypes of interneurons present within GG specimens and the expression and cellular distribution patterns of
GABA receptors (GABAR) and
GABA transporter 1 (GAT1). The expression of the various components of the
GABA-ergic system were also analyzed in the perilesional cortex. We investigated the expression of
parvalbumin,
calbindin,
calretinin,
GABA(A)R (a1 subunit)(,)
GABA(B) (R1 and R2) and GAT-1 using immunocytochemistry in 30 specimens of GG obtained during
epilepsy surgery, including 10 cases with sufficient amount of perilesional cortex. Immunocytochemistry for
calbindin (CB),
calretinin (CR) and
parvalbumin (PV) demonstrate the presence of inhibitory neurons of different subtypes within the GG specimens.
Calcium-binding protein-positive interneurons represent a small fraction of the total neuronal population. Both
GABA(A)R and
GABA(B)R (R1 and R2) subtypes were detected within the neuronal component of GG specimens. In addition,
GABA(B)R2 immunoreactivity (IR) was observed in glial cells. GG specimens displayed also expression of GAT-1 IR. Compared to normal cortex, the density of PV- and CB-immunoreactive interneurons was reduced in the perilesional cortex of GG patients, whereas CR-labeling was similar to that observed in normal cortex. GAT-1 IR was also significantly reduced in the perilesional specimens. The cellular distribution of components of the
GABA-ergic system in GG, together with the perilesional changes suggest that alterations of the
GABA-ergic system may contribute to the complex abnormal functional network of these highly epileptogenic developmental lesions.