title: Effects of behaviorally active ACTH (4-10) analogue - Semax on rat basal forebrain cholinergic neurons.
abstract: OBJECTIVE
  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 microM, Semax did not affect proliferation of glial cells in primary cultures.
  
  
  CONCLUSIONS
  Implications of these findings with respect to Alzheimer's disease remain to be clarified.
authors.affiliation: Institute of Molecular Genetics Russian Academy of Sciences, Kurchatov sq 2, 123182 Moscow, Russia. igorag@img.ras.ru
authors.forename: Igor A
authors.initials: IA
authors.lastname: Grivennikov
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Dolotov
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Zolotarev
authors.forename: Ludmila A
authors.initials: LA
authors.lastname: Andreeva
authors.forename: Nikolai F
authors.initials: NF
authors.lastname: Myasoedov
authors.forename: Lauren
authors.initials: L
authors.lastname: Leacher
authors.forename: Ira B
authors.initials: IB
authors.lastname: Black
authors.forename: Cheryl F
authors.initials: CF
authors.lastname: Dreyfus
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology*; D051381:Rats; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D005680:gamma-Aminobutyric Acid; C048487:ACTH (4-7), Pro-Gly-Pro-; D000324:Adrenocorticotropic Hormone; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase