The Program Project hypothesizes that the processes of progenitor proliferation, neural differentiation, axon extension and synapse formation are regulated by neuron-neuron and neuron-glial interactions. These cell-cell interactions, in turn, are mediated through the actions of multiple intercellular and intracellular signals that impact seemingly unrelated developmental events. Our studies will elucidate molecules and mechanisms that regulate proliferation, survival, differentiation and synaptogenesis in the developing brain. They focus on the roles of BDNF and Eph family members and lead us to increased understanding of how to effect brain repair and regeneration. Importantly, the studies move from the culture dish, to the developing brain in vivo. Moreover, they extend the work to analysis of a neurotherapeutic molecule used for women of child bearing age and young children. To achieve our goals, Project 1 will examine mechanisms by which the anticonvulsant, valproic acid affects development of neurons and glia, ranging from proliferation control to differentiation and release of BDNF from neurons and glia. Project 2 will explore an emerging field of signal interaction between Eph and Trk family receptors. Project 3 will define mechanisms underlying synaptic plasticity by examining the roles of cytoskeletal structures in transmitter receptor trafficking and spine enlargement/formation and shrinkage and their regulation by intracellular kinases and BDNF. Project 4 will explore mechanisms underlying the processing and release of pro- and mature isoforms of BDNF from neurons. Project 5 will examine mechanisms underlying astrocyte-neuron interaction mediated by the release and synthesis of BDNF. In sum, these interactive projects are designed to explore roles of BDNF in development and disease. Understanding the mechanisms underlying these processes may provide insights into therapeutic interventions that will impact diseases of the developing brain.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD023315-24
Application #
8307402
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (DC))
Program Officer
Grave, Gilman D
Project Start
1997-03-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
24
Fiscal Year
2012
Total Cost
$1,422,280
Indirect Cost
$212,582
Name
University of Medicine & Dentistry of NJ
Department
Neurosciences
Type
Schools of Medicine
DUNS #
617022384
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
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Yang, Jianmin; Harte-Hargrove, Lauren C; Siao, Chia-Jen et al. (2014) proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Cell Rep 7:796-806
Fulmer, Clifton G; VonDran, Melissa W; Stillman, Althea A et al. (2014) Astrocyte-derived BDNF supports myelin protein synthesis after cuprizone-induced demyelination. J Neurosci 34:8186-96
Bowling, Heather; Zhang, Guoan; Bhattacharya, Aditi et al. (2014) Antipsychotics activate mTORC1-dependent translation to enhance neuronal morphological complexity. Sci Signal 7:ra4
Sheleg, Michal; Yochum, Carrie L; Wagner, George C et al. (2013) Ephrin-A5 deficiency alters sensorimotor and monoaminergic development. Behav Brain Res 236:139-47
Das, Gitanjali; Reuhl, Kenneth; Zhou, Renping (2013) The Golgi-Cox method. Methods Mol Biol 1018:313-21
Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V et al. (2013) Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction. Nat Commun 4:2490
Lee, Chi Wai; Vitriol, Eric A; Shim, Sangwoo et al. (2013) Dynamic localization of G-actin during membrane protrusion in neuronal motility. Curr Biol 23:1046-56
Huang, Yangyang; Dreyfus, Cheryl F (2013) Culturing astrocytes from postnatal rats. Methods Mol Biol 1018:71-80
Rui, Yanfang; Myers, Kenneth R; Yu, Kuai et al. (2013) Activity-dependent regulation of dendritic growth and maintenance by glycogen synthase kinase 3*. Nat Commun 4:2628

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