Affiliations: Institute of Molecular Genetics Russian Academy of
Sciences, Kurchatov sq.2, 123182 Moscow, Russia | Department of Neuroscience and Cell Biology UMDNJ/
Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854,
USA
Note: [] Corresponding author: Igor A. Grivennikov, Laboratory of
Molecular Genetics of Somatic Cells, Institute of Molecular Genetics, Russian
Academy of Sciences, Kurchatov sq. 2, 123182 Moscow, Russia. Tel.: +7499
1960014; Fax: +7499 1960221; E-mail: igorag@img.ras.ru
Abstract: PURPOSE. It is well established that cholinergic neurons of the
basal forebrain degenerate in Alzheimer's dementia. Although recent studies
were concentrated on screening molecules that might reduce the concomitant cell
loss, little is known about therapeutically promising molecules. We studied the
effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro), a behaviorally active
adrenocorticotropic hormone (4–10) analogue, on survival of cholinergic basal
forebrain neurons in vitro. Semax is known to stimulate learning and
memory and can be successfully used for treatment of ischemic stroke. METHODS.
Primary cultures of neuronal and glial cells from basal forebrain of rats were
used in all experiments. The stability of Semax in cell cultures was tested by
HPLC analysis. Cell survival in neuronal cultures was quantitated using
immocytochemical and cytochemical analyses as well as detection of choline
acetyltransferase activity. RESULTS. We have shown that Semax may approximately
1.5–1.7 fold increase survival of cholinergic basal forebrain neurons in
vitro. Moreover, Semax (100 nM) stimulated activity of choline
acetyltransferase in dissociated basal forebrain tissue cultures. However, the
numbers of GABA-ergic neurons, total neuron specific enolase neurons were not
affected. In concentration from 1 nM to 10 μM, Semax did
not affect proliferation of glial cells in primary cultures. CONCLUSION.
Implications of these findings with respect to Alzheimer's disease remain to be
clarified.
