The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model

• Published in: Journal of psychopharmacology (Oxford) 2007-08, Vol.21 (6), p.611-619
• Main Authors: Ostrovskaya, Rita U., Gruden, Marina A., Bobkova, Natalya A., Sewell, Robert D. E., Gudasheva, Tatyana A., Samokhin, Alexander N., Seredinin, Sergey B., Noppe, Wim, Sherstnev, Vladimir V., Morozova-Roche, Ludmilla A.
• Format: Article
• Language: English
• Subjects: Aggregates; Alzheimer Disease - drug therapy; Alzheimer Disease - immunology; Alzheimer Disease - psychology; Alzheimer's disease; Amyloid beta-Peptides - immunology; Animal behavior; Animal memory; Animals; Antibodies; Autoantibodies - blood; Behavior, Animal - drug effects; Brain; Care and treatment; Cognitive ability; Cognitive enhancement; Dipeptides - pharmacology; Dipeptides - therapeutic use; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fibrillogenesis; Immune response; Immunoreactivity; Influence; Lysozyme; Male; Memory - drug effects; Memory tasks; Mice; Microscopy, Atomic Force; Muramidase - immunology; Nerve Growth Factors - immunology; Neurodegeneration; Neurodegenerative diseases; Neuronal-glial interactions; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurotoxicity; Nootropic Agents - pharmacology; Nootropic Agents - therapeutic use; Olfactory Bulb - surgery; Peptide Fragments - immunology; Peptides; Proline; Properties; Rodents; S100 Calcium Binding Protein beta Subunit; S100 Proteins - immunology; S100b protein; Smart drugs and nutrients; Space Perception - drug effects; Spatial analysis; Spatial discrimination; Spatial memory; Time Factors; β-Amyloid
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881106071335

The effects of the novel proline-containing nootropic and neuroprotective dipeptide, noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were investigated in NMRI mice following olfactory bulbectomy. We have shown previously that these animals developed Alzheimer's disease (AD)-like behaviour, morphology and biochemistry including impairment of spatial memory, regional neuronal degeneration and elevated Aβ peptide brain levels. In the current investigation, spatial memory was assessed using the Morris water maze and serum antibodies to in vitro morphologically characterized amyloid structures of both Aβ(25—35) peptide and equine lysozyme, as well as to neurotrophic glial factor S100b, were analyzed by enzyme-linked immunosorbent assay (ELISA). Noopept (administered at a dose of 0.01 mg/kg for a period of 21 days and during a further 5 days training) restored spatial memory and increased serum antibody levels to oligomers of Aβ(25—35) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Aβ(25—35) peptide prefibrillar aggregates was more marked in sham-operated compared to the bulbectomized subjects which were characterized by an overall suppression of immunoreactivity. Enhancement of the immune response to Aβ(25—35) peptide prefibrils caused by noopept may attenuate the neurotoxic consequences of amyloid fibrillization and also be associated with an improvement in spatial memory in bulbectomized mice. These actions of noopept, combined with it's previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.