title: The neurotoxic effects of N-methyl-N-nitrosourea on the electrophysiological property and visual signal transmission of rat's retina.
abstract: The neurotoxic effects of N-methyl-N-nitrosourea (MNU) on the inner retinal neurons and related visual signal circuits have not been described in any animal models or human, despite ample morphological evidences about the MNU induced photoreceptor (PR) degeneration. With the helping of MEA (multielectrode array) recording system, we gained the opportunity to systemically explore the neural activities and visual signal pathways of MNU administrated rats. Our MEA research identified remarkable alterations in the electrophysiological properties and firstly provided instructive information about the neurotoxicity of MNU that affects the signal transmission in the inner retina. Moreover, the spatial electrophysiological functions of retina were monitored and found that the focal PRs had different vulnerabilities to the MNU. The MNU-induced PR dysfunction exhibited a distinct spatial- and time-dependent progression. In contrast, the spiking activities of both central and peripheral RGCs altered synchronously in response to the MNU administration. Pharmacological tests suggested that gap junctions played a pivotal role in this homogeneous response of RGCs. SNR analysis of MNU treated retina suggested that the signaling efficiency and fidelity of inner retinal circuits have been ruined by this toxicant, although the microstructure of the inner retina seemed relatively consolidated. The present study provided an appropriate example of MEA investigations on the toxicant induced pathological models and the effects of the pharmacological compounds on neuron activities. The positional MEA information would enrich our knowledge about the pathology of MNU induced RP models, and eventually be instrumental for elucidating the underlying mechanism of human RP.
authors: Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853, PR China.
authors: Ye
authors: Y
authors: Tao
authors: Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Tao
authors: T
authors: Chen
authors: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an, PR China.
authors: Bei
authors: B
authors: Liu
authors: Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Guo Qing
authors: GQ
authors: Yang
authors: Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853, PR China.
authors: Guanghua
authors: G
authors: Peng
authors: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an, PR China.
authors: Hua
authors: H
authors: Zhang
authors: Department of Ophthalmology, General Hospital of Chinese PLA, Beijing 100853, PR China.
authors: Yi Fei
authors: YF
authors: Huang
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D004596:Electroretinography / Q000187:drug effects; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000477:Alkylating Agents; D008770:Methylnitrosourea
keywords: Electrophysiological; N-Methyl-N-nitrosourea; Neurotoxic; Photoreceptors; Retinitis pigmentosa; Visual signal