PMID- 16635254 OWN - NLM STAT- MEDLINE DCOM- 20060523 LR - 20131121 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 97 Suppl 1 DP - 2006 Apr TI - Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. PG - 82-6 AB - The heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is an analogue of the N-terminal fragment (4-10) of adrenocorticotropic hormone which, after intranasal application, has profound effects on learning and memory formation in rodents and humans, and also exerts marked neuroprotective effects. A clue to the molecular mechanism underlying this neurotropic action was recently given by the observation that Semax stimulates the synthesis of brain-derived neurotrophic factor (BDNF), a potent modulator of synaptic plasticity, in astrocytes cultured from rat basal forebrain. In the present study, we investigated whether Semax affects BDNF levels in rat basal forebrain upon intranasal application of the peptide. In addition, we examined whether cell membranes isolated from this brain region contained binding sites for Semax. The binding of tritium-labelled Semax was found to be time dependent, specific and reversible. Specific Semax binding required calcium ions and was characterized by a mean+/-SEM dissociation constant (KD) of 2.4+/-1.0 nm and a BMAX value of 33.5+/-7.9 fmol/mg protein. Sandwich immunoenzymatic analysis revealed that Semax applied intranasally at 50 and 250 microg/kg bodyweight resulted in a rapid increase in BDNF levels after 3 h in the basal forebrain, but not in the cerebellum. These results point to the presence of specific binding sites for Semax in the rat basal forebrain. In addition, these findings indicate that the cognitive effects exerted by Semax might be associated, at least in part, with increased BDNF protein levels in this brain region. FAU - Dolotov, Oleg V AU - Dolotov OV AD - Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russian Federation. FAU - Karpenko, Ekaterina A AU - Karpenko EA FAU - Seredenina, Tamara S AU - Seredenina TS FAU - Inozemtseva, Lyudmila S AU - Inozemtseva LS FAU - Levitskaya, Natalia G AU - Levitskaya NG FAU - Zolotarev, Yuriy A AU - Zolotarev YA FAU - Kamensky, Andrey A AU - Kamensky AA FAU - Grivennikov, Igor A AU - Grivennikov IA FAU - Engele, Juergen AU - Engele J FAU - Myasoedov, Nikolay F AU - Myasoedov NF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Peptide Fragments) RN - 0 (RNA, Messenger) RN - 10028-17-8 (Tritium) RN - 42Z2K6ZL8P (Manganese) RN - 80714-61-0 (ACTH (4-7), Pro-Gly-Pro-) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - SY7Q814VUP (Calcium) SB - IM MH - Administration, Intranasal MH - Adrenocorticotropic Hormone/*analogs & derivatives/metabolism/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Calcium/pharmacology MH - Cell Membrane/metabolism MH - Cells, Cultured MH - Immunoenzyme Techniques MH - Male MH - Manganese/pharmacology MH - *Neuroprotective Agents/metabolism/pharmacology MH - Peptide Fragments/*metabolism/*pharmacology MH - Prosencephalon/*drug effects/*metabolism MH - RNA, Messenger/analysis MH - Rats MH - Rats, Wistar MH - Tritium EDAT- 2006/04/26 09:00 MHDA- 2006/05/24 09:00 CRDT- 2006/04/26 09:00 PHST- 2006/04/26 09:00 [pubmed] PHST- 2006/05/24 09:00 [medline] PHST- 2006/04/26 09:00 [entrez] AID - JNC3658 [pii] AID - 10.1111/j.1471-4159.2006.03658.x [doi] PST - ppublish SO - J Neurochem. 2006 Apr;97 Suppl 1:82-6. doi: 10.1111/j.1471-4159.2006.03658.x.