Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain

J Neurochem. 2006 Apr;97 Suppl 1:82-6. doi: 10.1111/j.1471-4159.2006.03658.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adrenocorticotropic Hormone / analogs & derivatives*
  • Adrenocorticotropic Hormone / metabolism
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Calcium / pharmacology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Immunoenzyme Techniques
  • Male
  • Manganese / pharmacology
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology*
  • Prosencephalon / drug effects*
  • Prosencephalon / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Tritium


  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Peptide Fragments
  • RNA, Messenger
  • Tritium
  • Manganese
  • ACTH (4-7), Pro-Gly-Pro-
  • Adrenocorticotropic Hormone
  • Calcium