Brain-Derived Neurotrophic Factor Induces Cell Survival and the Migration of Murine Adult Hippocampal Precursor Cells During Differentiation In Vitro.
The generation of new neurons during adulthood involves local precursor cell migration and terminal differentiation in the dentate gyrus. These events are influenced by the hippocampal microenvironment. Brain-derived neurotrophic factor (BDNF) is relevant for hippocampal neuronal development and behavior. Interestingly, studies that have been performed in controlled in vitro systems that involve isolated precursor cells that were derived from the dentate gyrus (AHPCs) have shown that BDNF induces the activation of the TrkB receptor and, consequentially, might activate signaling pathways that favor survival and neuronal differentiation. Based on the fact that the cellular events of AHPCs that are induced by single factors can be studied in this controlled in vitro system, we investigated the ability of BDNF and the involvement of protein kinase C (PKC), as one of the TrkB-downstream activated signaling proteins, in the regulation of migration, here reflected by motility, of AHPCs. Precursor cells were cultured following a concentration-response curve (1-640 ng/ml) for 24 or 96 h. We found that BDNF favored cell survival without altering the viability under culture proliferative conditions of the AHPCs. Concomitantly, glial- and neuronal-differentiated precursor cells increased as a consequence of survival promoted by BDNF. Additionally, pharmacological approaches showed that BDNF (40 ng/ml)-induced migration of AHPCs was blocked with the compounds K252a and GF109203x, which prevent the activation of TrkB and PKC, respectively. The results indicate that in the in vitro migration of differentiated AHPCs it is involved the BDNF and TrkB cascade. Our results provide additional information about the mechanism by which BDNF impacts adult neurogenesis in the hippocampus.
Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada México-Xochimilco No. 101, Colonia San Lorenzo Huipulco, Delegación Tlalpan, C.P. 14370, Mexico City, Mexico.
Leonardo
L
Ortiz-López
Laboratory of Neuropsychopharmacology, Division of Neurosciences, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370, Mexico City, Mexico.
Nelly Maritza
NM
Vega-Rivera
Advanced Health Sciences Pavilion, Cedars-Sinai, 127 S. San Vicente Boulevard, Los Angeles, CA, 90048, USA.
Harish
H
Babu
Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada México-Xochimilco No. 101, Colonia San Lorenzo Huipulco, Delegación Tlalpan, C.P. 14370, Mexico City, Mexico. gbernabe@imp.edu.mx.
Gerardo Bernabé
GB
Ramírez-Rodríguez
D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D026121:Indole Alkaloids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007211:Indoles; D008301:Maleimides; C049985:staurosporine aglycone; D020813:Receptor, trkB; D011493:Protein Kinase C; C070515:bisindolylmaleimide I
Adult neurogenesis; BDNF; Cell survival; Hippocampus; Migration; Neural precursor cells; Protein kinase C
PLoS One. 2007 Apr 25;2(4):e388
17460755
Dev Neurobiol. 2010 Apr;70(5):304-22
20186705
J Biol Chem. 1993 Jul 25;268(21):15812-22
8340406
PLoS One. 2013;8(1):e55039
23383048
Neuroscience. 2014 Feb 28;260:158-70
24361917
Mol Cell Neurosci. 2006 Mar;31(3):560-73
16426857
Learn Mem. 1999 May-Jun;6(3):243-56
10492006
Trends Neurosci. 2004 Aug;27(8):447-52
15271491
Nat Neurosci. 1999 Mar;2(3):266-70
10195220
Mol Cell Neurosci. 1997;8(6):389-404
9143557
J Neurochem. 2004 May;89(4):844-52
15140184
Biochem Soc Trans. 2014 Dec;42(6):1477-83
25399557
Mol Neurodegener. 2009 Dec 21;4:52
20025751
Oncogene. 2001 Nov 1;20(50):7398-407
11704869
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1319-24
16432194
J Neurosci. 2000 Sep 15;20(18):7116-21
10995859
Nat Rev Neurosci. 2000 Dec;1(3):191-8
11257907
Nat Neurosci. 2000 Apr;3(4):342-9
10725923
Eur J Neurosci. 2004 Nov;20(10):2580-90
15548201
Annu Rev Neurosci. 1996;19:463-89
8833451
Nat Rev Neurosci. 2006 Sep;7(9):697-709
16924259
Mol Psychiatry. 2010 Jan;15(1):80-92
19621014
Neuropsychopharmacology. 2009 Aug;34(9):2180-91
19421166
Development. 2002 Mar;129(6):1435-42
11880352
J Pineal Res. 2007 Mar;42(2):180-90
17286751
Nat Neurosci. 2007 Sep;10(9):1110-5
17726477
J Biol Chem. 2000 Apr 7;275(14):10697-701
10744767
Cell. 2002 Nov 1;111(3):293-303
12419241
J Cell Physiol. 2012 May;227(5):2123-9
21769870
Neuron. 2004 May 27;42(4):535-52
15157417
J Comp Neurol. 1997 Feb 3;378(1):135-57
9120052
J Cell Sci. 2001 Oct;114(Pt 20):3583-90
11707510
Hippocampus. 2008;18(5):435-9
18240316
Annu Rev Neurosci. 1999;22:295-318
10202541
Front Neurosci. 2009 Sep 30;3:49
20582276
Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L429-38
10956616
Nature. 1997 Apr 3;386(6624):493-5
9087407
J Neurosci. 2012 Oct 10;32(41):14318-30
23055503
Neuron. 2009 Sep 24;63(6):761-73
19778506
J Neurosci. 2013 Apr 3;33(14 ):6112-22
23554492
Dev Neurobiol. 2012 Jun;72(6):943-52
22252978
J Neurosci. 2005 Feb 2;25(5):1089-94
15689544