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

ABSTRACT

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. 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. 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. 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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Agmatine
• scopolamine, memory retrieval
• hippocampus
• CaMKII-α
• mice

Acknowledgments

This work was supported by grants No. 19554 and 17506 from Shiraz University of Medical Sciences, Shiraz, Iran. The findings were partly extracted from a thesis written by Dr. Nahid Baberi.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical statement

The protocols were approved by the Animals Experiment Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.MED.REC.1399.048 and IR.SUMS.REC.1398.811). The present article does not contain any experiments on human participants performed by any of the authors.

Additional information

Funding

This work was supported by grants No. 19554 and 17506 from Shiraz University of Medical Sciences, shiraz, Iran.