Purchase this article with an account.
Tamas Atlasz, Yi Zhang, Dora Reglodi, Stewart Bloomfield, Bela Volgyi; Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Prevents Monosodium Glutamate (MSG) Induced Functional Disturbances in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1950.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Exogenously applied MSG binds to glutamate receptors and provokes a chronic activation of postsynaptic neurons, thereby exerting excitotoxic effects. We studied the short term functional consequences of MSG treatment in the mouse retina. In addition, we investigated whether administration of PACAP1-38, a potent neuroprotective peptide, could rescue retinal ganglion cells (RGCs) from MSG-induced excitotoxic effects.
Spontaneous and light-evoked spikes of RGCs from wild type mice were recorded using a 60-channel multielectrode array (Multichannel Systems GmbH). Green ( = 527nm) light was used to generate full field stimuli. Retinas were treated with MSG (10 mM) or a mixture of MSG + PACAP1-38 (10 μM; 15 min) or MSG + PACAP1-38 antagonist PACAP6-38 (1µM; 15 min) + PACAP1-38. Data were analyzed using the Off-line Sorter/NeuroExplorer software package (Plexon, USA).
MSG exerted physiologically detectable effects on RGCs only when applied at a concentration >10 mM. These included a characteristic increase of spontaneous spiking 4-5 minutes after drug application. During this time, spike correlations between RGC pairs were reduced. However, after 10-15 minutes of MSG application, the spontaneous activity of most RGCs was dramatically reduced or totally eliminated. Pretreatment with PACAP1-38 prevented the MSG effects as indicated by little or no change in the spontaneous spiking patterns during the course of recordings (up to 60 minutes). In addition to the changes in RGC spontaneous spiking, MSG blocked the light-evoked responses of all recorded cells. The light-evoked responses of approximately 40% of RGCs were retained following pretreatment with PACAP1-38. The protective effects of PACAP1-38 on both spontaneous and light-evoked RGC spikes were reduced by application of the antagonist PACAP6-38.
We found that MSG had clear short term effects on the spontaneous and light-evoked spiking of mouse RGCs. Application of PACAP1-38, well-known for its long term neuroprotective effects, also rescued RGCs from the short term MSG-induced insults. We propose that PACAP1-38 exerts its protective effects either through desensitization of postsynaptic glutamate receptors and/or the extrusion of excess glutamate from the synaptic gap.
This PDF is available to Subscribers Only