Relationship between Sigma-1 receptor and BDNF in the visual system.
Relationship between Sigma-1 receptor and BDNF in the visual system.
复制标题
DOI：
10.1016/j.exer.2017.10.012
复制
发表时间：
2018-03
影响因子：
3.4
通讯作者：
Bollinger KE
中科院分区：
文献类型：
--
作者：
Mysona BA;Zhao J;Smith S;Bollinger KE
青光眼是一种无法治愈的视神经病变，其特征在于视网膜神经节细胞（RGC）的功能障碍和死亡。脑源性神经营养因子（BDNF）是一种重要的神经营养因子，支持RGC的功能和生存。尽管BDNF的重要性，我们的知识，调节BDNF的加工和分泌的分子机制是不完整的。σ-1受体（S1 R）与海马中BDNF的增加以及脑源性星形胶质细胞和神经元细胞系的BDNF分泌相关。关于S1 R和BDNF在视觉系统中的关系知之甚少。在这里，我们研究如何S1 R激活和缺失改变表达的成熟BDNF（mBDNF）和proBDNF在视网膜和培养的视神经乳头（ONH）星形胶质细胞。对于S1 R活化，通过腹膜内注射向C57 BL/6 J小鼠施用S1 R激动剂（+）-喷他佐辛（PTZ，0.5mg/kg），每周3次，持续5周。还在S1 R敲除和年龄匹配的C57 BL/6 J小鼠中检测proBDNF和mBDNF的表达。在体外，用3μM PTZ处理培养的ONH星形胶质细胞24小时，然后收集培养基和ONH星形胶质细胞裂解物。结果显示，（+）-PTZ处理增加视网膜和海马中的mBDNF蛋白。相反，S1 R缺失与视网膜mBDNF缺陷相关。在ONH星形胶质细胞中，S1 R激动剂（+）-PTZ显著增加细胞裂解物中分泌的BDNF和proBDNF的水平。这些发现支持S1 R在视网膜和视神经乳头内调节BDNF水平中的作用。用S1 R激动剂治疗可能通过增加内源性BDNF水平而对青光眼等疾病有益。
Glaucoma is an incurable optic neuropathy characterized by dysfunction and death of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an essential neurotrophin that supports RGC function and survival. Despite BDNF’s importance, our knowledge of molecular mechanisms that modulate BDNF processing and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. Much less is known about the relationship between S1R and BDNF in the visual system. Here, we examine how S1R activation and deletion alter expression of mature BDNF (mBDNF) and proBDNF in retina and cultured optic nerve head (ONH) astrocytes. For S1R activation, the S1R agonist (+)-pentazocine (PTZ, 0.5 mg/kg) was administered by intraperitoneal injection to C57BL/6J mice, 3 times per week, for 5 weeks. Expression of proBDNF and mBDNF was also examined in S1R knockout and age-matched C57BL/6J mice. In vitro, cultured ONH astrocytes were treated with 3μM PTZ for 24 hours followed by collection of media and ONH astrocyte lysates. Results showed that treatment with (+)-PTZ increased mBDNF protein in both retina and hippocampus. In contrast, S1R deletion was associated with retinal mBDNF deficits. In ONH astrocytes S1R agonist (+)-PTZ significantly increased levels of secreted BDNF and proBDNF in cell lysates. These findings support a role for S1R in the modulation of BDNF levels within the retina and optic nerve head. Treatment with S1R agonists might provide benefit in diseases such as glaucoma by increasing BDNF levels from endogenous sources.
登录
查看更多内容
影响因子：
2.3
作者：
Fujimoto, Michiko;Hayashi, Teruo;Urfer, Roman;Mita, Shiro;Su, Tsung-Ping
通讯作者：
Su, Tsung-Ping
影响因子：
4.4
作者：
Johnson, Elaine C.;Jia, Lijun;Morrison, John C.
通讯作者：
Morrison, John C.
影响因子：
25
作者：
Matsumoto, Tomoya;Rauskolb, Stefanie;Barde, Yves-Alain
通讯作者：
Barde, Yves-Alain
影响因子：
6.2
作者：
Beckel, Jonathan M.;Argall, Arthur J.;Lim, Jason C.;Xia, Jingsheng;Lu, Wennan;Coffey, Erin E.;Macarak, Edward J.;Shahidullah, Mohammed;Delamere, Nicholas A.;Zode, Gulab S.;Sheffield, Val C.;Shestopalov, Valery I.;Laties, Alan M.;Mitchell, Claire H.
通讯作者：
Mitchell, Claire H.
影响因子：
4.4
作者：
Ha, Yonju;Saul, Alan;Smith, Sylvia B.
通讯作者：
Smith, Sylvia B.