PMID- 23320097
OWN - NLM
STAT- MEDLINE
DCOM- 20130815
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 1
DP  - 2013
TI  - Neurogenic and neurotrophic effects of BDNF peptides in mouse hippocampal primary 
      neuronal cell cultures.
PG  - e53596
LID - 10.1371/journal.pone.0053596 [doi]
LID - e53596
AB  - 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.
FAU - Cardenas-Aguayo, Maria del Carmen
AU  - Cardenas-Aguayo Mdel C
AD  - Department of Neurochemistry, New York State Institute for Basic Research in 
      Developmental Disabilities, Staten Island, New York, United States of America.
FAU - Kazim, Syed Faraz
AU  - Kazim SF
FAU - Grundke-Iqbal, Inge
AU  - Grundke-Iqbal I
FAU - Iqbal, Khalid
AU  - Iqbal K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130108
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*physiology
MH  - Cells, Cultured
MH  - Hippocampus/*cytology/drug effects/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/metabolism/*physiology
MH  - Neurogenesis/drug effects/*physiology
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/metabolism/pharmacology
MH  - Oligopeptides/genetics/metabolism/pharmacology
MH  - Peptide Fragments/genetics/*physiology
MH  - Receptor, trkB/agonists/antagonists & inhibitors/metabolism
PMC - PMC3539976
COIS- Competing Interests: Studies described in this article were supported in part by 
      the New York State Office of Peoplewith Developmental Disabilities, and a 
      research grant from EVER NeuroPharma GmbH, Unterach, Austria. This does not alter 
      the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials.
EDAT- 2013/01/16 06:00
MHDA- 2013/08/16 06:00
PMCR- 2013/01/08
CRDT- 2013/01/16 06:00
PHST- 2012/08/14 00:00 [received]
PHST- 2012/11/30 00:00 [accepted]
PHST- 2013/01/16 06:00 [entrez]
PHST- 2013/01/16 06:00 [pubmed]
PHST- 2013/08/16 06:00 [medline]
PHST- 2013/01/08 00:00 [pmc-release]
AID - PONE-D-12-24497 [pii]
AID - 10.1371/journal.pone.0053596 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(1):e53596. doi: 10.1371/journal.pone.0053596. Epub 2013 Jan 8.