Neurogenic and neurotrophic effects of BDNF peptides in mouse hippocampal primary neuronal cell cultures

• Published in: PloS one 2013-01, Vol.8 (1), p.e53596
• Main Authors: Cardenas-Aguayo, Maria del Carmen, Kazim, Syed Faraz, Grundke-Iqbal, Inge, Iqbal, Khalid
• Format: Article
• Language: English
• Subjects: Adults; Alzheimer's disease; Amino Acid Sequence; Amino acids; Analysis; Animals; Anxiety; Autism; Biology; Biomarkers - metabolism; Brain; Brain research; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - physiology; Cell culture; Cell death; Cell survival; Cells, Cultured; Developmental disabilities; Disease; Embryos; Health aspects; Hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Hydrogen peroxide; Kinases; Lymphocytes B; Memory; Mental depression; Mice; Molecular Sequence Data; Movement disorders; Nerve Growth Factors - metabolism; Nerve Growth Factors - physiology; Nervous system; Neurochemistry; Neurodegenerative diseases; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neurological disorders; Neurons; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; Oligopeptides - genetics; Oligopeptides - metabolism; Oligopeptides - pharmacology; Parkinson's disease; Peptide Fragments - genetics; Peptide Fragments - physiology; Peptides; Permeability; Phosphorylation; Positive feedback; Receptor, trkB - agonists; Receptor, trkB - antagonists & inhibitors; Receptor, trkB - metabolism; Rodents; Signaling; Trends; TrkB receptors; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053596

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.