Abstract
Focal cortical dysplasia (FCD) is a common cause of pharmacologically-intractable epilepsy, however, the precise mechanisms underlying the epileptogenicity of FCD remains to be determined. Neuropeptide Y (NPY), an endogenous anticonvulsant in the central nervous system, plays an important role in the regulation of neuronal excitability. Increased expression of NPY and its receptors has been identified in the hippocampus of patients with mesial temporal lobe epilepsy, presumed to act as an endogenous anticonvulsant mechanism. Therefore, we investigated whether expression changes in NPY receptors occurs in patients with FCD. We specifically investigated the expression of seizure-related NPY receptor subtypes Y1, Y2, and Y5 in patients with FCD versus autopsy controls. We found that Y1R and Y2R were up-regulated at the mRNA and protein levels in the temporal and frontal lobes in FCD lesions. By contrast, there was no significant change in either receptor detected in parietal lesions. Notably, overexpression of Y5R was consistently observed in all FCD lesions. Our results demonstrate the altered expression of Y1R, Y2R and Y5R occurs in FCD lesions within the temporal, frontal and parietal lobe. Abnormal NPY receptor subtype expression may be associated with the onset and progression of epileptic activity and may act as a therapeutic candidate for the treatment of refractory epilepsy caused by FCD.
Highlights
Focal cortical dysplasia (FCD) is a malformation of cortical development commonly associated with medically refractory epilepsy
We found that Y1R and Y2R were upregulated at the mRNA and protein levels in the temporal and frontal lobes in FCD lesions
Abnormal Neuropeptide Y (NPY) receptor subtype expression may be associated with the onset and progression of epileptic activity and may act as a therapeutic candidate for the treatment of refractory epilepsy caused by FCD
Summary
Focal cortical dysplasia (FCD) is a malformation of cortical development commonly associated with medically refractory epilepsy. Seizure-induced upregulation in the synthesis and release of NPY as well as altered expression of NPY receptors in hippocampus are generally believed to represent a compensatory anticonvulsant response In keeping with this hypothesis, Thom et al [4] reported a striking increase in the density of NPY immunoreactive fibers plexus in FCD, which may represent an adaptive anti-epileptic mechanism to dampen down seizure propagation. It still remains unclear which NPY receptor subtypes are responsible for mediating the anticonvulsant effect of NPY in the neocortex. Our data provided a basic understanding of the plasticity of NPY receptors in patients with FCD
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