Vol.:(0123456789) 1 3 Molecular Biology Reports (2019) 46:489–496 https://doi.org/10.1007/s11033-018-4501-4 ORIGINAL ARTICLE The neuroprotective efect of agmatine against amyloid β-induced apoptosis in primary cultured hippocampal cells involving ERK, Akt/ GSK-3β, and TNF-α Etrat Hooshmandi 1,2  · Rasoul Ghasemi 3,4  · Parisa Iloun 3,4  · Maryam Moosavi 5,6 Received: 25 August 2018 / Accepted: 13 November 2018 / Published online: 24 November 2018 © Springer Nature B.V. 2018 Abstract β-Amyloid peptide (Aβ), the major element of senile plaques in Alzheimer’s disease (AD), has been found to accumulate in brain regions critical for memory and cognition. Deposits of Aβ trigger neurotoxic events which lead to neural apoptotic death. The present study examined whether agmatine, an endogenous polyamine formed by the decarboxylation of L-arginine, possesses a neuroprotective efect against Aβ-induced toxicity. Primary rat hippocampal cells extracted from the brains of 18–19-day-old embryos were exposed to 10 µM of Aβ (25–35) in the absence or presence of agmatine at 150 or 250 µM. Additionally, the involvement of Akt (Protein Kinae B), GSK-3β (glycogen synthase kinase 3-β), ERK (Extracellular Signal- Regulated Kinase) and TNF-α (Tumor necrosis factor-α) in the agmatine protection against Aβ-induced neurotoxicity was investigated. Agmatine signifcantly prevented the efect of Aβ exposure on cell viability and caspase-3 assays. Furthermore, agmatine considerably restored Aβ-induced decline of phospho-Akt and phospho-GSK and blocked Aβ-induced increase of phospho-ERK and TNF-alpha. Taken together, these fndings might shed light on the protective efect of agmatine as a potential therapeutic agent for AD. Keywords Beta amyloid · Hippocampal cell culture · Agmatine · Akt/GSK3β · ERK · TNF-α Abbreviations AD Alzheimer’s disease Akt Protein Kinae B GSK-3β Glycogen synthase kinase 3-β ERK Extracellular Signal-Regulated Kinase TNF-α Tumor necrosis factor-α Aβ Amyloid β protein HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid MTT 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetra- zolium bromide RIPA Radioimmunoprecipitation assay DMSO Dimethyl sulfoxide PBS Phosphate-bufered saline PVDF Polyvinylidene difuoride Etrat Hooshmandi and Rasoul Ghasemi contributed equally to this work and should be considered as co-frst authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-018-4501-4) contains supplementary material, which is available to authorized users. * Maryam Moosavi marmoosavi@sums.ac.ir Etrat Hooshmandi ehoshmandi@sbmu.ac.ir Rasoul Ghasemi Rghasemi60@sbmu.ac.ir Parisa Iloun p_iloun@sbmu.ac.ir 1 Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 3 Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 5 Shiraz Nuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 6 Nanobiology and Nanomedicine Research Centre, Shiraz University of Medical sciences, Shiraz, Iran