The neuroprotective effect of agmatine against amyloid β-induced apoptosis in primary cultured hippocampal cells involving ERK, Akt/GSK-3β, and TNF-α

  • Etrat Hooshmandi
  • Rasoul Ghasemi
  • Parisa Iloun
  • Maryam Moosavi
Original Article


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 effect 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 significantly prevented the effect 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 findings might shed light on the protective effect of agmatine as a potential therapeutic agent for AD.


Beta amyloid Hippocampal cell culture Agmatine Akt/GSK3β ERK TNF-α 



Alzheimer’s disease


Protein Kinae B


Glycogen synthase kinase 3-β


Extracellular Signal-Regulated Kinase


Tumor necrosis factor-α

Amyloid β protein


4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid


3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide


Radioimmunoprecipitation assay


Dimethyl sulfoxide


Phosphate-buffered saline


Polyvinylidene difluoride


Bovine serum albumin


One-way analysis of variance



This work was supported by a Grant (No. 90-01-55-4206) from Shiraz University of Medical Sciences, Shiraz, Iran.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

11033_2018_4501_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 KB)
11033_2018_4501_MOESM2_ESM.docx (14 kb)
Supplementary material 2 (DOCX 14 KB)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Neuroscience Research CenterShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Clinical Neurology Research CenterShiraz University of Medical SciencesShirazIran
  3. 3.Department of Physiology, Faculty of MedicineShahid Beheshti University of Medical SciencesTehranIran
  4. 4.Neurophysiology Research CenterShahid Beheshti University of Medical SciencesTehranIran
  5. 5.Shiraz Nuroscience Research CenterShiraz University of Medical SciencesShirazIran
  6. 6.Nanobiology and Nanomedicine Research CentreShiraz University of Medical sciencesShirazIran

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