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Progressive Effects of Sildenafil on Visual Processing in Rats.
Neuroscience ( IF 2.9 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.neuroscience.2020.06.033
Freja Gam Østergaard 1 , Alex R Wade 2 , Hartwig Roman Siebner 3 , Kenneth Vielsted Christensen 4 , Bettina Laursen 1
Affiliation  

Photoreceptors are light-sensitive cells in the retina converting visual stimuli into electrochemical signals. These signals are evaluated and interpreted in the visual pathway, a process referred to as visual processing. Phosphodiesterase type 5 and 6 (PDE5 and 6) are abundant enzymes in retinal vessels and notably photoreceptors where PDE6 is exclusively present. The effects of the PDE inhibitor sildenafil on the visual system, have been studied using electroretinography and a variety of clinical visual tasks. Here we evaluate effects of sildenafil administration by electrophysiological recordings of flash visual evoked potentials (VEPs) and steady-state visual evoked potentials (SSVEPs) from key regions in the rodent visual pathway. Progressive changes were investigated in female Sprague-Dawley rats at 10 timepoints from 30 min to 28 h after peroral administration of sildenafil (50 mg/kg). Sildenafil caused a significant reduction in the amplitude of VEPs in both visual cortex and superior colliculus, and a significant delay of the VEPs as demonstrated by increased latency of several VEP peaks. Also, sildenafil-treatment significantly reduced the signal-to-noise ratio of SSVEPs. The effects of sildenafil were dependent on the wavelength condition in both assays. Our results support the observation that while PDE6 is a key player in phototransduction, near full inhibition of PDE6 is not enough to abolish the complex process of visual processing. Taken together, VEPs and SSVEPs are effective in demonstrating progressive effects of drug-induced changes in visual processing in rats and as the same paradigms may be applied in humans, representing a promising tool for translational research.



中文翻译:

西地那非对大鼠视觉加工的进展作用。

感光器是视网膜中的光敏细胞,将视觉刺激转换为电化学信号。这些信号在视觉通道中被评估和解释,该过程称为视觉处理。5和6型磷酸二酯酶(PDE5和6)是视网膜血管中的丰富酶,尤其是仅存在PDE6的感光细胞。PDE抑制剂西地那非对视觉系统的影响已通过视网膜电图和各种临床视觉任务进行了研究。在这里,我们通过啮齿动物视觉途径中关键区域的闪光视觉诱发电位(VEP)和稳态视觉诱发电位(SSVEP)的电生理记录来评估西地那非给药的效果。口服西地那非(50 mg / kg)后30分钟至28小时的10个时间点,在雌性Sprague-Dawley大鼠中研究了进行性变化。西地那非导致视觉皮层和上丘的VEP幅度显着降低,并且VEP显着延迟,这表现为多个VEP峰潜伏期延长。此外,昔多芬治疗显着降低了SSVEP的信噪比。西地那非的作用取决于两种测定中的波长条件。我们的结果支持以下观察:虽然PDE6是光转导的关键参与者,但几乎完全抑制PDE6不足以消除视觉处理的复杂过程。在一起

更新日期:2020-07-14
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