Meyer J H, Gruol D L
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037.
Brain Res. 1994 Jan 7;633(1-2):253-61. doi: 10.1016/0006-8993(94)91546-6.
The influences of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) on neuronal properties and synaptic transmission in area CA1 of the hippocampus were examined using a slice preparation. DHEAS had no apparent effects upon cell membrane resistance or active cell responses to intracellular hyperpolarizing or depolarizing current pulses. However, DHEAS did increase the excitability of CA1 neurons in response to Schaffer collateral synaptic stimulation. This was apparent both in field potential recordings as well as intracellular recordings. Effects appeared within minutes following exposure to DHEAS and were reversible, suggesting a non-genomic mechanism of action. Intracellular recordings indicated that DHEAS increased the amplitudes of EPSPs associated with stimulation of Schaffer collateral fibers. The increased EPSP amplitudes resulted from DHEAS effecting an inhibition of fast IPSPs as well as a direct enhancement of excitatory synaptic transmission. No significant effects on slow IPSPs were noted. In summary, neurosteroids such as DHEAS may influence synaptic transmission through multiple mechanisms. Such influences result in increased excitability of postsynaptic neurons and indicate the profound influences neurosteroids may have to regulate neuronal activity in intact CNS structures.
利用脑片标本研究了神经甾体硫酸脱氢表雄酮（DHEAS）对海马CA1区神经元特性和突触传递的影响。DHEAS对细胞膜电阻或细胞对细胞内超极化或去极化电流脉冲的主动反应没有明显影响。然而，DHEAS确实增加了CA1神经元对Schaffer侧支突触刺激的兴奋性。这在场电位记录和细胞内记录中都很明显。暴露于DHEAS后几分钟内就出现了效应，且效应是可逆的，这表明其作用机制是非基因组的。细胞内记录表明，DHEAS增加了与Schaffer侧支纤维刺激相关的兴奋性突触后电位（EPSP）的幅度。EPSP幅度的增加是由于DHEAS抑制了快速抑制性突触后电位（IPSP）以及直接增强了兴奋性突触传递。未观察到对慢速IPSP有显著影响。总之，像DHEAS这样的神经甾体可能通过多种机制影响突触传递。这种影响导致突触后神经元兴奋性增加，并表明神经甾体可能对完整中枢神经系统结构中神经元活动的调节具有深远影响。
