(Core C) The overall objective of the core is to facilitate efficient preparation, distribution and analysis of ferret brain tissue among Projects 1-3 for studies of normal development and development following early hypoxic brain injury. The Ferret model has distinct advantages over existing rodent models for studies central to this program project focused on novel late migratory streams (Project 1), oligodendrocyte precursor cell development (Project 2) and hypoxia/HIF pathway signaling (Project 3). These advantages include: (1) a gyrencephalic brain with a protracted period of postnatal brain development and (2) the existence of a distinct outer subventricular zone and late migrating neuronal streams similar to human MMS and DMS. Core C will promote synergy and interaction among the three projects by facilitating integrated Ferret tissue utilization. We propose the following two specific objectives: Objective 1: Optimal preparation and utilization of brain tissue from a unique small animal, gyrencephalic model of normal cortical development in the ferret (Mustela putorius) Objective 2: Further develop a small animal model of human preterm white matter injury in the gyrencephalic ferret suitable for translational studies of pathogenesis and therapy. Unlike rodents, Ferrets are an FDA regulated species. The core will be responsible for developing and maintaining appropriate protocols for the compassionate care and use of Ferrets. All protocols will be developed in consultation with University of California, San Francisco Laboratory Animal Resource Center (LARC) veterinarians. The Core will maintain annual regulatory approval through the UCSF Institutional Animal Care and Use Committee (IUCUC). The Core will carry out all animal surgeries and postsurgical care along with LARC veterinarians. A major function of the core will be to organize efficient use of animal tissue by optimizing sharing of tissue among compatible projects. The Program Project Administrative Committee will determine allocation and prioritization of animals and tissue. The core will be responsible for developing and testing reagents and techniques for tissue analysis. Finally the core will develop conditions for the chronic hypoxia translational model of newborn brain injury. This will include Ferret brain MR imaging, an application with potential for increasing translational relevance by comparison with complementary human data.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
1P01NS083513-01A1
Application #
8742988
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Shiow, Lawrence R; Favrais, Geraldine; Schirmer, Lucas et al. (2017) Reactive astrocyte COX2-PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury. Glia 65:2024-2037
Watanabe, Momoko; Buth, Jessie E; Vishlaghi, Neda et al. (2017) Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection. Cell Rep 21:517-532
Sabo, Jennifer K; Heine, Vivi; Silbereis, John C et al. (2017) Olig1 is required for noggin-induced neonatal myelin repair. Ann Neurol 81:560-571
Lindquist, Robert A; Guinto, Cristina D; Rodas-Rodriguez, Jose L et al. (2016) Identification of proliferative progenitors associated with prominent postnatal growth of the pons. Nat Commun 7:11628
Tsai, Hui-Hsin; Niu, Jianqin; Munji, Roeben et al. (2016) Oligodendrocyte precursors migrate along vasculature in the developing nervous system. Science 351:379-84
Paredes, Mercedes F; Sorrells, Shawn F; Garcia-Verdugo, Jose M et al. (2016) Brain size and limits to adult neurogenesis. J Comp Neurol 524:646-64
Paredes, Mercedes F; James, David; Gil-Perotin, Sara et al. (2016) Extensive migration of young neurons into the infant human frontal lobe. Science 354:
Nobuta, Hiroko; Cilio, Maria Roberta; Danhaive, Olivier et al. (2015) Dysregulation of locus coeruleus development in congenital central hypoventilation syndrome. Acta Neuropathol 130:171-83
Lee, Hyun Kyoung; Chaboub, Lesley S; Zhu, Wenyi et al. (2015) Daam2-PIP5K is a regulatory pathway for Wnt signaling and therapeutic target for remyelination in the CNS. Neuron 85:1227-43
Tate, Matthew C; Lindquist, Robert A; Nguyen, Thuhien et al. (2015) Postnatal growth of the human pons: a morphometric and immunohistochemical analysis. J Comp Neurol 523:449-62

Showing the most recent 10 out of 11 publications