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Shreya Datta, Renee C Ryals, Aaron Coyner, Mark E Pennesi; Cell signaling pathways involved in 8-OH-DPAT dependent neuroprotection. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1987.
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Studies have shown that the 5-HT1A receptor agonist (±)-8-Hydroxy-2-dipropylaminotetralin (8-OH-DPAT) can protect the retina from light induced retinopathy. However, the downstream signaling pathways have yet to be elucidated. The purpose of these experiments was to investigate the signaling pathways involved in neuroprotection associated with 5HT1A receptor activation.
Two-month-old BALB/c mice were injected intraperitoneally (IP) with 8-OH-DPAT (10 mg/kg). Naïve (un-injected) mice and saline injected mice served as controls. At 1h, 6h, 24h and 48h post-injection retinas were harvested and total protein was extracted. SDS-PAGE electrophoresis was performed using 30 µg of total retinal protein from each animal to study the temporal kinetics of signaling pathways. Blots were probed with cell signaling antibodies specific to Erk1/2, phospho-Erk1/2, Akt, phospho-Akt, STAT3 and phospho-STAT3 antibodies.
Western blot analysis showed presence of total Erk1/2, STAT3 and Akt at all time points tested. At 1h, 6h, 24h and 48h post-injection there was no activation of STAT3. At 1h, 6h, 24h and 48h there was activation of both Erk1/2 and Akt. However, activation was the same in control retinas and experimental retinas.
One IP injection of 8-OH-DPAT did not activate STAT3 nor did it alter activation of Erk1/2 or Akt. Future studies will examine these same pathways after multiple IP injections of 8-OH-DPAT consistent with reported administration of this drug in light induced retinopathy models. In addition, alternative signaling pathways will be investigated for their role in 5-HT1A specific neuroprotection.
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