Expression of angiogenic and neurotrophic factors in the progenitor cell niche of adult monkey subventricular zone.
The subventricular zone along the anterior horn (SVZa) of the cerebral lateral ventricle of adult mammals contains multipotent progenitor cells, which supposedly exist in an angiogenic niche. Numerous signals are known to modulate the precursor cell proliferation, migration or differentiation, in rodent models. In contrast, the data on signals regulating the primate SVZa precursors in vivo are scarce. We analyzed the expression at protein level of a panel of angiogenic and/or neurotrophic factors and their receptors in SVZa of adult macaque monkeys, under normal condition or after transient global ischemia which enhances endogenous progenitor cell proliferation. We found that fms-like tyrosine kinase 1 (Flt1), a receptor for vascular endothelial cell growth factor, was expressed by over 30% of the proliferating progenitors, and the number of Flt1-positive precursors was significantly increased by the ischemic insult. Smaller fractions of mitotic progenitors were positive for the neurotrophin receptor tropomyosin-related kinase (Trk) B or the hematopoietic receptor Kit, while immature neurons expressed Flt1 and the neurotrophin receptor TrkA. Further, SVZa astroglia, ependymal cells and blood vessels were positive for distinctive sets of ligands/receptors, which we characterized. The presented data provide a molecular phenotypic analysis of cell types comprising adult monkey SVZa, and suggest that a complex network of angiogenic/neurotrophic signals operating in an autocrine or paracrine manner may regulate SVZa neurogenesis in the adult primate brain.
Tonchev
A B
AB
Department of Restorative Neurosurgery, Division of Neuroscience, Kanazawa University Graduate School of Medical Science, Takara-machi 13-1, Kanazawa 920-8641, Japan.
Yamashima
T
T
Guo
J
J
Chaldakov
G N
GN
Takakura
N
N
D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism; D008251:Macaca; D018919:Neovascularization, Physiologic / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013687:Telencephalon / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D042501:Angiogenic Proteins; D009414:Nerve Growth Factors; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D019009:Proto-Oncogene Proteins c-kit; D020917:Receptor, trkA; D020813:Receptor, trkB; D040281:Vascular Endothelial Growth Factor Receptor-1