title: Neurogenic and neurotrophic effects of BDNF peptides in mouse hippocampal primary neuronal cell cultures.
abstract: The level of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is down regulated in Alzheimer's disease (AD), Parkinson's disease (PD), depression, stress, and anxiety; conversely the level of this neurotrophin is increased in autism spectrum disorders. Thus, modulating the level of BDNF can be a potential therapeutic approach for nervous system pathologies. In the present study, we designed five different tetra peptides (peptides B-1 to B-5) corresponding to different active regions of BDNF. These tetra peptides were found to be non-toxic, and they induced the expression of neuronal markers in mouse embryonic day 18 (E18) primary hippocampal neuronal cultures. Additionally, peptide B-5 induced the expression of BDNF and its receptor, TrkB, suggesting a positive feedback mechanism. The BDNF peptides induced only a moderate activation (phosphorylation at Tyr 706) of the TrkB receptor, which could be blocked by the Trk's inhibitor, K252a. Peptide B-3, when combined with BDNF, potentiated the survival effect of this neurotrophin on H(2)O(2)-treated E18 hippocampal cells. Peptides B-3 and B-5 were found to work as partial agonists and as partial antagonists competing with BDNF to activate the TrkB receptor in a dose-dependent manner. Taken together, these results suggest that the described BDNF tetra peptides are neurotrophic, can modulate BDNF signaling in a partial agonist/antagonist way, and offer a novel therapeutic approach to neural pathologies where BDNF levels are dysregulated.
authors: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, United States of America.
authors: Maria del Carmen
authors: Mdel C
authors: Cardenas-Aguayo
authors: Syed Faraz
authors: SF
authors: Kazim
authors: Inge
authors: I
authors: Grundke-Iqbal
authors: Khalid
authors: K
authors: Iqbal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D020813:Receptor, trkB / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D020813:Receptor, trkB