Effect of weak combined static and extremely low-frequency alternating magnetic fields on spatial memory and brain amyloid-ß in two animal models of Alzheimer's disease.

Subchronic effect of a weak combined magnetic field (MF), produced by superimposing a constant component, 42 µT and an alternating MF of 0.08 µT, which was the sum of two frequencies of 4.38 and 4.88 Hz, was studied in olfactory bulbectomized (OBE) and transgenic Tg (APPswe, PSEN1) mice, which were used as animal models of sporadic and heritable Alzheimer's disease (AD) accordingly. Spatial memory was tested in a Morris water maze on the following day after completion of training trials with the hidden platform removed. The amyloid-ß (Aß) level was determined in extracts of the cortex and hippocampus of mice using a specific DOT analysis while the number and dimensions of amyloid plaques were detected after their staining with thioflavin S in transgenic animals. Exposure to the MFs (4 h/day for 10 days) induced the decrease of Aß level in brain of OBE mice and reduced the number of Aß plaques in the cortex and hippocampus of Tg animals. However, memory improvement was revealed in Tg mice only, but not in the OBE animals. Here, we suggest that in order to prevent the Aß accumulation, MFs could be used at early stage of neuronal degeneration in case of AD and other diseases with amyloid protein deposition in other tissues.

Synthetic Fragment of Receptor for Advanced Glycation End Products Prevents Memory Loss and Protects Brain Neurons in Olfactory Bulbectomized Mice.

Activation of receptor for advanced glycation end products (RAGE) plays an essential role in the development of Alzheimer's disease (AD). It is known that the soluble isoform of the receptor binds to ligands and prevents negative effects of the receptor activation. We proposed that peptide fragments from RAGE prevent negative effects of the receptor activation during AD neurodegeneration. We have synthesized peptide fragments from surface-exposed regions of RAGE. Peptides were intranasally administrated into olfactory bulbectomized (OBX) mice, which developed some characteristics similar to AD neurodegeneration. We have found that only insertion of fragment (60-76) prevents the memory of OBX mice. Immunization of OBX mice with peptides showed that again only (60-76) peptide protected the memory of animals. Both intranasal insertion and immunization decreased the amyloid-ß (Aß) level in the brain. Activity of shortened fragments of (60-76) peptide was tested and showed only the (60-70) peptide is responsible for manifestation of activity. Intranasal administration of (60-76) peptide shows most protective effect on morpho-functional characteristics of neurons in the cortex and hippocampal areas. Using Flu-(60-76) peptide, we revealed its penetration in the brain of OBX mice as well as colocalization of Flu-labeled peptide with Aß in the brain regions in transgenic mice. Flu-(60-76) peptide complex with trimer of Aß was detected by SDS-PAGE. These data indicate that Aß can be one of the molecular target of (60-70) peptide. These findings provide a new peptide molecule for design of anti-AD drug and for investigation of RAGE activation ways in progression of AD neurodegeneration.