Cell-cell communication represents the combined effects of multiple polypeptide factors. To explain complex effects in the nervous system requires an understanding of how local circuits and signal transduction pathways are integrated. Ephrins and Neurotrophins display both rapid and slower long lasting effects that require receptor signaling to proceed in a linear stop-wise fashion, but also influence each other, either directiy or through signaling intermediates. Regulation of Ephrins and Neurotrophins is likely to be determined by the additive effects of their receptors and the duration of second messengers and phosphorylation events. Interactions between Ephrin and Neurotrophin receptors and downstream signaling proteins provide a mechanism for merging the actions of different ligand-receptor systems in order to achieve novel cellular outcomes. This subproject will focus on a set of downstream substrates that are used by both Ephrin and Neurotrophin receptors. The hypothesis is that cooperativity and antagonism between these two different transmembrane protein systems provide additional mechanisms for extracellular signaling. The proposed research is relevant to the understanding and treatment of early developmental disorders, such as autism, and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis, which depend upon the actions of Ephrins and Neurotrophins for correct developmental patterning and circuit formation.

Public Health Relevance

Ephrins and Neurotrophlns represent major polypeptide factors that influence many aspects ofthe nervous system, including growth cone guidance, axonal growth and higher order activities, such as synaptic plasticity. BDNF and ephrins are involved in synapse modification and hippocampal neural activity. The study of the combined effects of neurotrophins and ephrins will help to understand their roles during development and degenerative diseases, such as Alzheimer's disease and spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD023315-23
Application #
8307395
Study Section
Special Emphasis Panel (ZHD1)
Project Start
Project End
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
23
Fiscal Year
2011
Total Cost
$410,854
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
DUNS #
617022384
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
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Bowling, Heather; Bhattacharya, Aditi; Klann, Eric et al. (2016) Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology. Neural Regen Res 11:363-7
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Lee, Hee Jae; Dreyfus, Cheryl; DiCicco-Bloom, Emanuel (2016) Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat. Dev Neurobiol 76:780-98
Bowling, Heather; Bhattacharya, Aditi; Zhang, Guoan et al. (2016) BONLAC: A combinatorial proteomic technique to measure stimulus-induced translational profiles in brain slices. Neuropharmacology 100:76-89
Mony, Tamanna Jahan; Lee, Jae Won; Dreyfus, Cheryl et al. (2016) Valproic Acid Exposure during Early Postnatal Gliogenesis Leads to Autistic-like Behaviors in Rats. Clin Psychopharmacol Neurosci 14:338-344
Das, Gitanjali; Yu, Qili; Hui, Ryan et al. (2016) EphA5 and EphA6: regulation of neuronal and spine morphology. Cell Biosci 6:48
Ma, Qian; Yang, Jianmin; Li, Thomas et al. (2015) Selective reduction of striatal mature BDNF without induction of proBDNF in the zQ175 mouse model of Huntington's disease. Neurobiol Dis 82:466-477
Anastasia, Agustin; Barker, Phillip A; Chao, Moses V et al. (2015) Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and Activation. J Neurosci 35:11911-20
Sheleg, Michal; Yochum, Carrie L; Richardson, Jason R et al. (2015) Ephrin-A5 regulates inter-male aggression in mice. Behav Brain Res 286:300-7

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