DOI: 10.1002/alz.072825 ISSN: 1552-5260

Cholinergic deficit induced memory retrieval deficit and hippocampal CaMKII‐alpha deregulation is counteracted by sub‐chronic agmatine treatment in mice

Vahid Reza Ostovan, Nahid Baberi, Majid Reza Farrokhi, Leila Moezi, Fatema Pirsalami, Roksana SoukhakLari, Maryam Moosavi
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology

Abstract

Background

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disease characterized by brain cholinergic dysfunction. Evidence suggests the impairment of memory retrieval phase in AD. It has been shown that CaMKII‐α expressing neurons are selectively reduced in the hippocampus in AD brains. The present study aimed to investigate the effect of scopolamine on the memory retrieval phase and the hippocampal CaMKII‐α signaling. In addition, the effect of sub‐chronic administration of agmatine against scopolamine induced memory and possible hippocampal CaMKII‐α deregulation was investigated in mice.

Method

Adult male NMRI mice were administered with agmatine at the doses of 5, 10, 20, 30 and 40 mg/kg/i.p. or saline for 11 days. Acquisition and retrieval tests of passive avoidance task were performed on days 10 and 11, respectively (30 Min following agmatine treatment). Scopolamine (1 mg/kg/i.p.) was administered once, 30 Min before retrieval test. Upon completion of the behavioral tasks, the hippocampi were isolated for western blot analysis to detect the phosphorylated and total levels of CaMKII‐α and beta actin proteins.

Result

The results showed that scopolamine induced memory retrieval deficit and decreased the phosphorylated level of hippocampal CaMKII‐α. Sub‐chronic agmatine treatment at the dose of 40 mg/kg prevented scopolamine induced memory retrieval deficit and restored the level of hippocampal phosphorylated CaMKII‐α.

Conclusion

This study suggests that hippocampal CaMKII‐α might play a role in scopolamine induced amnesia and sub‐chronic agmatine prevents the impairing effect of scopolamine on the retrieval phase of memory and the phosphorylation of hippocampal CaMKII‐α protein.

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