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. 2016 Mar 29;7(13):15329-38.
doi: 10.18632/oncotarget.7855.

Altered expression of neuropeptide Y receptors caused by focal cortical dysplasia in human intractable epilepsy

Lin Li  1   2   3 , Jiahui Deng  1   2   3 , Changqing Liu  1 , Hanjiang Luo  4 , Yuguang Guan  1 , Jian Zhou  1 , Xueling Qi  1 , Tianfu Li  2   3 , Zhiqing David Xu  3   4   5 , Guo-Ming Luan  1   2   3
Affiliations

Altered expression of neuropeptide Y receptors caused by focal cortical dysplasia in human intractable epilepsy

Lin Li et al. Oncotarget. .

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.

Keywords: Pathology Section; focal cortical dysplasia; neuropeptide Y Y1 receptor; neuropeptide Y Y2 receptor; neuropeptide Y Y5 receptor.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. The expression and distribution of Y1R in different cortical lobes of FCD patients
A.-C. Representative images show Y1R (green) and DAPI (blue) in temporal lobe (A), frontal lobe (B) and parietal lobe (C) with upper panels showing control and lower panels showing patients. The last images are the enlarged views from areas indicated by squares. C, control; P, patient. D. The quantification of Y1R fluorescent intensities of A-C. E. Representative Western blots of Y1R proteins in the temporal, frontal and parietal lobe. F. Bar graphs show quantitative data for Y1R signals that are normalized to GAPDH signal. G. Quantitative PCR array analysis of the expression of Y1R in the temporal, frontal and parietal lobe. Data are expressed by means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 compared with control group.
Figure 2
Figure 2. The expression and distribution of Y2R in different cortical lobes of FCD patients
A.-C. Immunofluorescent images illustrate Y2R (green) and DAPI (blue) in temporal lobe (A), frontal lobe (B) and parietal lobe (C) with upper panels showing control and lower panels showing patients. The last images are the enlarged views from areas indicated by squares. C, control; P, patient. D. The quantification of Y2R fluorescent intensities of A-C. E. Representative Western blots of Y2R proteins in the temporal, frontal and parietal lobe. F. Bar graphs show quantitative data for Y2R signals that are normalized to GAPDH signal. G. Quantitative PCR array analysis of the expression of Y2R in the temporal, frontal and parietal lobe. Data are expressed by means ± SEM. *P < 0.05, **P < 0.01, compared with control group.
Figure 3
Figure 3. The expression and distribution of Y5R in different cortical lobes of FCD patients
A.-C. Representative images show Y5R (green) and DAPI (blue) in temporal lobe (A), frontal lobe (B) and parietal lobe (C) of control (upper panels) and patients (lower panels). The last images are the enlarged views from areas indicated by squares. C, control; P, patient. D. The quantification of Y5R fluorescent intensities of A-C. E. Representative Western blots of Y5R proteins in the temporal, frontal and parietal lobe. F. Bar graphs show quantitative data for Y5R signals that are normalized to GAPDH signal. G. Quantitative PCR array analysis of the expression of Y5R in the temporal, frontal and parietal lobe. Data are expressed by means ± SEM. *P < 0.05 compared with control group.
Figure 4
Figure 4. The expression of NPY was increased in different cortical lobes of FCD patients
A.-C. Immunofluorescent images show NPY (green) and DAPI (blue) in temporal lobe (A), frontal lobe (B) and parietal lobe (C) with upper panels showing controls and lower panels showing patients. C: control; P: patient. D. The quantification of NPY fluorescent intensities of A-C. E. Representative Western blots show NPY protein expression in the temporal, frontal and parietal lobe. F. Bar graphs show quantitative data for NPY signals that are normalized to GAPDH signal. G. Quantitative PCR array analysis of the expression of NPY in the temporal, frontal and parietal lobe. Data are expressed by means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 compared with control group.
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