Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH-GTS-21, and rAAV-mediated α7 nicotinic receptor gene transfer
- 作者：Jeffrey S. Thinschmidt ; Gretchen Y. Ló ; pez-Herná ; ndez ; Ke Ren ; Michael A. King ; Edwin M. Meyer ; Roger L. Papke
- 关键词：
ttp ; //www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 ; Gene transfer ; Nicotinic ; rAAV ; Hippocampus ; 5-hydroxyindole (5-HI) ; GTS-21 ; DMXB
- 刊名：Brain Research
- 出版年：2008
- 期刊代码：8_00068993
- 类别：neu
- 出版时间：8 April 2008
- 卷：1203
- 期：Complete
- 页码：51-60
- 文件大小：772 K
摘要
One approach to treatment of negative cognitive effects associated with Alzheimer's disease and schizophrenia may involve activation of neuronal ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 nicotinic acetylcholine receptors (nAChRs). We used the ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7-selective partial agonist 3-(4-hydroxy, 2-methoxy-benzylidene)anabaseine (4OH-GTS-21), the ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 modulator 5-hydroxyindole (5-HI), and recombinant adeno-associated virus (rAAV)-mediated ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 gene transfer in order to test the hypothesis whether combining these strategies would significantly increase indirect measures of ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 nAChR function, including measures of spontaneous synaptic events in CA1 pyramidal cells. 5-HI (1 mM), and 5-HI (1 mM) + 4OH-GTS-21 (5 μM) increased the frequency of APV- and NBQX-sensitive currents, while 5-HI + 4OH-GTS-21 increased the frequency and amplitude of bicuculline-sensitive currents. Effects on EPSCs were blocked with tetrodotoxin (TTX) (1 μM), but not by methyllycaconitine (MLA) (50 nM). Neither TTX nor MLA reduced the potentiation of IPSC frequencies. However, TTX blocked, and in some cases MLA reduced, the potentiation of IPSC amplitudes. These data suggest that effects of 5-HI + 4OH-GTS-21 on EPSC frequency were associated with action potential-dependent transmitter release produced by 5HI, and that potentiation of IPSC amplitudes resulted at least in part, from activation of ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 nAChRs. Finally, rAAV-mediated ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 gene transfer did not alter the magnitude of effects produced by 5-HI or 5-HI + 4OH-GTS-21. Thus, although we previously showed that direct measures of ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 nAChR function were enhanced by ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 gene transfer, indirect measures of ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 nAChRs function were not significantly enhanced by combining ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 gene transfer with either agonist activation or positive allosteric modulation of ttp://www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">7 nAChRs.