Ca2+-permeable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma

被引:14
|
作者
Kitaura, Hiroki [1 ]
Sonoda, Masaki [2 ]
Teramoto, Sayaka [3 ]
Shirozu, Hiroshi [2 ]
Shimizu, Hiroshi [1 ]
Kimura, Tadashi [1 ]
Masuda, Hiroshi [2 ]
Ito, Yosuke [2 ]
Takahashi, Hitoshi [1 ]
Kwak, Shin [3 ]
Kameyama, Shigeki [2 ]
Kakita, Akiyoshi [1 ]
机构
[1] Univ Niigata, Dept Pathol, Brain Res Inst, Niigata, Japan
[2] Nishi Niigata Chuo Natl Hosp, Dept Neurosurg, Niigata, Japan
[3] Univ Tokyo, Ctr Dis Biol & Integrat Med, Grad Sch Med, Bunkyo Ku, Tokyo, Japan
关键词
Hypothalamic hamartoma; Human tissue; ADAR2; RNA editing; Joro Spider Toxin; MOTOR-NEURONS; RNA; CHANNELS; DEATH;
D O I
10.1111/epi.13700
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca2+ permeability through -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues. In HH, however, these activities were clearly abolished by application of Joro Spider Toxin (JSTX), a specific inhibitor of the Ca2+-permeable AMPA receptor. Consistent with these physiologic findings, the neuronal nuclei showed disappearance of adenosine deaminase acting on RNA 2 (ADAR2) immunoreactivity. Furthermore, examination of glutamate receptor 2 (GluA2) messenger RNA (mRNA) revealed that editing efficiency at the glutamine/arginine site was significantly low. These results suggest that neurons in HH may bear Ca2+-permeable AMPA receptors due to dislocation of ADAR2.
引用
收藏
页码:E59 / E63
页数:5
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