title: VEGF-dependent and PDGF-dependent dynamic neurovascular reconstruction in the neurohypophysis of adult mice.
abstract: Hypothalamo-neurohypophysial system (HNS) releases arginine vasopressin (AVP) and oxytocin (OXT) from axonal terminals of the neurohypophysis (NH) into blood circulation for controlling body fluid homeostasis and lactation. Chronic osmotic and suckling stimulations have been shown to cause neurovascular and neuroglial reconstruction in the NH of adult mammals and no study has been reported for vascular dynamics. The aim of this study was to elucidate the occurrence of continuous angiogenesis and growth factor-dependent neurovascular reconstruction in the NH of adult mice. Active proliferation of endothelial cells and oligodendrocyte progenitor cells (OPCs) was observed using the immunohistochemistry of bromodeoxyuridine and Ki-67. Vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2 (KDR)) were highly expressed at pituicytes and endothelial cells respectively. Moreover, prominent expression of platelet-derived growth factor B (PDGFB) and PDGF receptor beta was observed at OXT-containing axonal terminals and pericytes respectively. Administration of the selective tyrosine kinase inhibitor AZD2171 for VEGFRs and STI571 for PDGFRs significantly decreased proliferation of endothelial cells and OPCs. Moreover, AZD2171 treatment decreased vascular density by facilitating apoptosis of endothelial cells and the withdrawal of its treatment led to remarkable rebound proliferation of endothelial cells, so that vascular density rapidly returned to normal levels. AZD2171 decreased the density of both AVP- and OXT-containing axonal terminals, whereas STI571 selectively decreased the density of AVP-containing ones. Thus, this study demonstrates that the signaling pathways of VEGF and PDGF are crucial mediators for determining proliferation of endothelial cells and OPCs and the density of AVP- and OXT-containing axonal terminals in the HNS.
authors.affiliation: Department of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Furube
authors.affiliation: Department of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mannari
authors.affiliation: Department of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, JapanDepartment of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Department of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Department of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Department of Applied BiologyKyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, JapanDepartment of Anatomy and NeuroscienceFaculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan smiyata@kit.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Miyata
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000098:blood supply* / Q000166:cytology* / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D007211:Indoles
chemical_list: D001127:Arginine Vasopressin; D010121:Oxytocin; D010982:Platelet-Derived Growth Factor; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C500926:cediranib; D007211:Indoles
keywords: angiogenesis; endothelial cell; neurosecretion; oxytocin; plasticity; vasopressin