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Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro.

Martins J, Elvas F, Brudzewsky D, Martins T, Kolomiets B, Tralhão P, Gøtzsche CR, Cavadas C, Castelo-Branco M, Woldbye DP, Picaud S, Santiago AR, Ambrósio AF - ASN Neuro (2015)

Bottom Line: We found that NPY attenuated the increase in the [Ca2+]i triggered by glutamate mainly via Y1 receptor activation.Using in vitro cultures of rat retinal explants exposed to NMDA, we found that NPY pretreatment prevented NMDA-induced cell death.In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal.

No MeSH data available.


Related in: MedlinePlus

The Y1 and Y5 receptor agonist (Leu31, Pro34) − NPY increases the response of OFF-type RGCs to light offset. (a) RGC spontaneous spiking rate quantification after the application of 1 µM NPY, 1 µM (Leu31, Pro34) − NPY, 1 µM NPY13–36, or a drug-free solution (control) for 10 min and upon 60 min of washout was recorded in ex vivo retinas using a MEA. A decrease in RGC spiking rate was observed over time, though no effects were found for drug treatments. (b) Examples of peri-stimulus time histograms and raster plots for ON-type RGC and OFF-type RGC responses are shown for seven consecutive stimulus blocks. White rectangles indicate duration of light period. (c) Quantification of initial burst to light onset of ON-type RGCs after application of the same drug treatments as in (a). No effect was found for the different drug treatments compared with control. (d) Quantification of initial burst to light offset of OFF-type RGCs after application of the same drug treatments as in (a). The application of 1 µM (Leu31, Pro34) − NPY for 10 min was able to increase the magnitude of OFF-type response compared with control. All data were normalized to the values obtained before drug application (baseline). Data are presented as mean ± SEM of n = 3 to 4 independent experiments. *p < .05, compared with control. Kruskal-Wallis followed by Dunn’s test.
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fig4-1759091415598292: The Y1 and Y5 receptor agonist (Leu31, Pro34) − NPY increases the response of OFF-type RGCs to light offset. (a) RGC spontaneous spiking rate quantification after the application of 1 µM NPY, 1 µM (Leu31, Pro34) − NPY, 1 µM NPY13–36, or a drug-free solution (control) for 10 min and upon 60 min of washout was recorded in ex vivo retinas using a MEA. A decrease in RGC spiking rate was observed over time, though no effects were found for drug treatments. (b) Examples of peri-stimulus time histograms and raster plots for ON-type RGC and OFF-type RGC responses are shown for seven consecutive stimulus blocks. White rectangles indicate duration of light period. (c) Quantification of initial burst to light onset of ON-type RGCs after application of the same drug treatments as in (a). No effect was found for the different drug treatments compared with control. (d) Quantification of initial burst to light offset of OFF-type RGCs after application of the same drug treatments as in (a). The application of 1 µM (Leu31, Pro34) − NPY for 10 min was able to increase the magnitude of OFF-type response compared with control. All data were normalized to the values obtained before drug application (baseline). Data are presented as mean ± SEM of n = 3 to 4 independent experiments. *p < .05, compared with control. Kruskal-Wallis followed by Dunn’s test.

Mentions: Since NPY is able to modulate neuronal activity in various brain regions (Silva et al., 2002; Benarroch, 2009), we hypothesized whether application of NPY to ex vivo retinas could directly modulate RGC spiking activity. For this purpose, we used a MEA system, which allows simultaneous recording spiking activity from various RGCs. After spike sorting based on template matching, the spiking rate for individual RGCs was quantified. In the first set of experiments, we recorded RGC spontaneous activity (no stimulus) before (baseline) and after the application of NPY (1 µM, n = 4 retinas), the Y1/Y5 agonist (Leu31, Pro34) − NPY (1 µM, n = 3), the Y2 agonist NPY13–36 (1 µM, n = 3), or a drug-free solution (control, n = 3) for 10 min under continuous perfusion (Figure 4(a)). In addition, a period of washout up to 60 min was included. We found a small decrease in RGC spiking rate over time reaching 79.5 ± 7.2% of baseline in control at 60 min of washout. However, exposure to NPY or NPY receptor agonists caused no effect since RGCs presented a decrease in spiking rate similar to control.Figure 4.


Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro.

Martins J, Elvas F, Brudzewsky D, Martins T, Kolomiets B, Tralhão P, Gøtzsche CR, Cavadas C, Castelo-Branco M, Woldbye DP, Picaud S, Santiago AR, Ambrósio AF - ASN Neuro (2015)

The Y1 and Y5 receptor agonist (Leu31, Pro34) − NPY increases the response of OFF-type RGCs to light offset. (a) RGC spontaneous spiking rate quantification after the application of 1 µM NPY, 1 µM (Leu31, Pro34) − NPY, 1 µM NPY13–36, or a drug-free solution (control) for 10 min and upon 60 min of washout was recorded in ex vivo retinas using a MEA. A decrease in RGC spiking rate was observed over time, though no effects were found for drug treatments. (b) Examples of peri-stimulus time histograms and raster plots for ON-type RGC and OFF-type RGC responses are shown for seven consecutive stimulus blocks. White rectangles indicate duration of light period. (c) Quantification of initial burst to light onset of ON-type RGCs after application of the same drug treatments as in (a). No effect was found for the different drug treatments compared with control. (d) Quantification of initial burst to light offset of OFF-type RGCs after application of the same drug treatments as in (a). The application of 1 µM (Leu31, Pro34) − NPY for 10 min was able to increase the magnitude of OFF-type response compared with control. All data were normalized to the values obtained before drug application (baseline). Data are presented as mean ± SEM of n = 3 to 4 independent experiments. *p < .05, compared with control. Kruskal-Wallis followed by Dunn’s test.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4552225&req=5

fig4-1759091415598292: The Y1 and Y5 receptor agonist (Leu31, Pro34) − NPY increases the response of OFF-type RGCs to light offset. (a) RGC spontaneous spiking rate quantification after the application of 1 µM NPY, 1 µM (Leu31, Pro34) − NPY, 1 µM NPY13–36, or a drug-free solution (control) for 10 min and upon 60 min of washout was recorded in ex vivo retinas using a MEA. A decrease in RGC spiking rate was observed over time, though no effects were found for drug treatments. (b) Examples of peri-stimulus time histograms and raster plots for ON-type RGC and OFF-type RGC responses are shown for seven consecutive stimulus blocks. White rectangles indicate duration of light period. (c) Quantification of initial burst to light onset of ON-type RGCs after application of the same drug treatments as in (a). No effect was found for the different drug treatments compared with control. (d) Quantification of initial burst to light offset of OFF-type RGCs after application of the same drug treatments as in (a). The application of 1 µM (Leu31, Pro34) − NPY for 10 min was able to increase the magnitude of OFF-type response compared with control. All data were normalized to the values obtained before drug application (baseline). Data are presented as mean ± SEM of n = 3 to 4 independent experiments. *p < .05, compared with control. Kruskal-Wallis followed by Dunn’s test.
Mentions: Since NPY is able to modulate neuronal activity in various brain regions (Silva et al., 2002; Benarroch, 2009), we hypothesized whether application of NPY to ex vivo retinas could directly modulate RGC spiking activity. For this purpose, we used a MEA system, which allows simultaneous recording spiking activity from various RGCs. After spike sorting based on template matching, the spiking rate for individual RGCs was quantified. In the first set of experiments, we recorded RGC spontaneous activity (no stimulus) before (baseline) and after the application of NPY (1 µM, n = 4 retinas), the Y1/Y5 agonist (Leu31, Pro34) − NPY (1 µM, n = 3), the Y2 agonist NPY13–36 (1 µM, n = 3), or a drug-free solution (control, n = 3) for 10 min under continuous perfusion (Figure 4(a)). In addition, a period of washout up to 60 min was included. We found a small decrease in RGC spiking rate over time reaching 79.5 ± 7.2% of baseline in control at 60 min of washout. However, exposure to NPY or NPY receptor agonists caused no effect since RGCs presented a decrease in spiking rate similar to control.Figure 4.

Bottom Line: We found that NPY attenuated the increase in the [Ca2+]i triggered by glutamate mainly via Y1 receptor activation.Using in vitro cultures of rat retinal explants exposed to NMDA, we found that NPY pretreatment prevented NMDA-induced cell death.In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal.

No MeSH data available.


Related in: MedlinePlus