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

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.

The memory modulatory effect of agmatine in passive avoidance task coincides with alterations of hippocampal CaMKII-α and ERK signaling in mice.

Agmatine is a polyamine suggested to act as a supposed neurotransmitter in the brain. Evidence has indicated that acute agmatine administration might modulate memory. The present study aimed to investigate the effect of repeated agmatine treatment on passive avoidance memory, hippocampal calcium-calmodulin-dependent protein kinase II-alpha (CaMKII-α), and Extracellular Signal-Regulated Kinase (ERK) signaling pathways in naive mice. Adult male NMRI mice were treated with agmatine (10, 20, 30, 40, and 80 mg/kg/ip) or saline for 11 days. Acquisition and retention tests of passive avoidance memory were performed on days 10 and 11, respectively. Following the memory retention test, the hippocampi were assessed for the levels of CaMKII-α and ERK using the western blotting technique. The results revealed the dose-dependent effect of agmatine on the passive avoidance memory. Accordingly, the memory was impaired in lower doses, but was improved in higher ones. Agmatine in none of the doses affected the nociception of the mice in tail-flick test. Furthermore, agmatine increased the phosphorylation of CaMKII-α and ERK in the hippocampus at memory enhancing doses, while ERK phosphorylation decreased following the impairing doses of agmatine. Thus, the dose-dependent effect of agmatine on memory might be related to its modulatory effect on CaMKII-α and ERK signal transduction, eventually regulating the memory process.

Developing Criteria for Lumbar Spine Magnetic Resonance Imaging (MRI) Using RAND Appropriateness Method (RAM).

BACKGROUND: Studies show that a large proportion of healthcare offered may be inappropriate or unnecessary. Magnetic resonance imaging (MRI) is a new and expensive diagnostic technology which has been increasingly used all over the world. Moreover, this trend has been more rapidly increasing in Iran. Low back pain is a common disorder all over the world and MRI technique is one of the several ways to assess its cause. OBJECTIVES: The present study aims to develop scenarios for lumbar spine MRI. MATERIALS AND METHODS: In the present study, the RAND Appropriateness Method (RAM) was used in order to reach consensus regarding developing scenarios for lumbar spine MRI. We generated scenarios from valid clinical guidelines as well as the experts' opinion. The panel members included nine specialists from various medical specialties that had scored scenarios in two rounds, the first of which was without interaction, while the second one was with interaction. RESULTS: We extracted 97 scenarios for the lumbar spine MRI in the scenario extracting phase of the study and the panel members added 18 scenarios. After implementation of two rounds, the scenarios were categorized into three ranges. Sixty seven (58%) of the scenarios were considered as appropriate, 45 (39%) as uncertain, and three (2.6%) as inappropriate. CONCLUSIONS: RAM is useful for identifying stakeholder views in settings with limited resources. Since RAM has precise instructions for consensus developing, a large number of scenarios were considered as uncertain. Therefore, more research has to be conducted on the issue.