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

¹ V. V. Zakusov State Institute of Pharmacology, Moscow, Russia.
² P. K. Anokhin State Institute of Normal Physiology, Moscow, Russia.
³ Institute of Cell Biophysics, Moscow Region, Puschino, Russia.
⁴ Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
⁵ Interdisciplinary Research Center, Campus Kortrijk, KU Keuven, Kortrijk, Belgium.
⁶ Department of Medical Biochemistry and Biophysics, Ume University, Ume, Sweden.

^* To whom correspondence should be addressed.

	Abstract

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 A 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 A_(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 A_(25-35) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to A_(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 A_(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.

Key Words: noopept (GVS-111), memory improvement, olfactory bulbectomy, Alzheimer's disease, antibodies, A_(25-35) peptide, amyloid

First published on November 8, 2006, doi:10.1177/0269881106071335

Journal of Psychopharmacology 2007;21:611.

A more recent version of this article appeared on August 1, 2007


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