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P3‐423: Neurogenic and neuroprotective effects of BDNF peptides in mouse hippocampal primary neuronal cell cultures
Author(s) -
Carmen CardenasAguayo Maria,
GrundkeIqbal Inge,
Iqbal Khalid
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1867
Subject(s) - synapsin i , tropomyosin receptor kinase b , neuroprotection , neurotrophic factors , neurotrophin , synapsin , brain derived neurotrophic factor , biology , neun , microbiology and biotechnology , neurite , neuroscience , trk receptor , receptor , immunology , immunohistochemistry , biochemistry , vesicle , membrane , synaptic vesicle , in vitro
Background: Disruption of growth factor signaling is a characteristic of many neurodegenerative disorders. The use of neurotrophic factors to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach. BDNF, a member of the neurotrophin family, is of particular interest, since the signaling pathway of its receptors trkB and p75 are known to promote survival, differentiation and synaptic function. In Alzheimer’s Disease (AD) the expression levels of BDNF are reduced. Since BDNF has short plasma half-life, and a poor BBB penetration, small molecules that could mimic the functions of BDNF, might be an alternative approach. The aim of this study is the evaluation of the potential neurogenic/ neurotrophic role of BDNF peptides in primary neuronal cell cultures. Methods: Via epitope mapping of neutralizing antibodies of the active region of BDNF we identified five tetrameric peptides. To screen them we used primary neuronal cell cultures from E18 C57BL/6 mouse hippocampus. After 5 days of treatment with the peptides or BDNF cells were fixed for immunohistochemistry, or protein were extracted for western blot. Antibodies for neuronal markers: TUJ1, NF-M, MAP-2, Synapsin I and NeuN, and for glial markers: GFAP. Viability was assayed with AlamarBlue. To analyze the activation of the TrkB, we used NIH 3T3 cells, stably transfected with the trkB receptor.Results:We found no toxic effect of the peptides B-1 to B-5 in primary neuronal cells. Peptides B-3> B-4> B-5 induced the neuronal marker neurofilament M and the synaptic marker synapsin I. Peptide B-3 had neuroprotective tendency against H2O2-induced toxicity. The activation of TrkB receptor by these peptides was analyzed in the fibroblast expressing TrkB. We found that peptides B-5 and B-3 induced the expression of TrkB. The activation of the TrkB by the peptides B-5 and B-3 was low as compared to the activation with BDNF. Conclusions: The present study demonstrates that peptides B-5, B-4 and B-3, corresponding to an active region of BDNF are able to induce the expression of neuronal markers and might be neuroprotective against H2O2-toxicity. These findings suggest the potential therapeutic use of these peptides in neurodegenerative diseases such as AD and other cognitive disorders.