Abstract

In this Supplement, we will be investigating whether the BDNF prodomain with a human SNP has biological activity within the AD brain, based on the premise that the prodomain and its co- receptors (p75NTR and SorCS2) are up-regulated in the AD brain. The ongoing scope of this grant has focused on a developmental period, peri-adolescence, when this ligand and receptor complex initially are co-expressed in the hippocampus. These proposed studies in the AD mouse model will assess whether the in vivo biological activity of the BDNF prodomain contributes to the altered neuronal and behavioral phenotypes in an AD mouse models at a later developmental time point. These proposed studies would suggest a reconceptualization of the biological role of this growth factor in AD that has been previously focused on loss of the mature form of BDNF leading to altered neuronal function in AD.

Public Health Relevance

In this Supplement, we will be investigating whether the BDNF prodomain with a human SNP has biological activity within the AD brain, based on the premise that the prodomain and its co- receptors (p75NTR and SorCS2) are up-regulated in the AD brain.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS052819-13S1
Application #
9718512
Study Section
Program Officer
Mamounas, Laura
Project Start
2018-09-18
Project End
2019-08-31
Budget Start
2018-09-18
Budget End
2019-08-31
Support Year
13
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Weill Medical College of Cornell University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Gray, J D; Rubin, T G; Kogan, J F et al. (2018) Translational profiling of stress-induced neuroplasticity in the CA3 pyramidal neurons of BDNF Val66Met mice. Mol Psychiatry 23:904-913
Giza, Joanna I; Kim, Jihye; Meyer, Heidi C et al. (2018) The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear Extinction Circuitry and Behavior. Neuron 99:1356
Giza, Joanna I; Kim, Jihye; Meyer, Heidi C et al. (2018) The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear Extinction Circuitry and Behavior. Neuron 99:163-178.e6
Jing, Deqiang; Lee, Francis S; Ninan, Ipe (2017) The BDNF Val66Met polymorphism enhances glutamatergic transmission but diminishes activity-dependent synaptic plasticity in the dorsolateral striatum. Neuropharmacology 112:84-93
Song, M; Martinowich, K; Lee, F S (2017) BDNF at the synapse: why location matters. Mol Psychiatry 22:1370-1375
Amadio, Patrizia; Colombo, Gualtiero I; Tarantino, Eva et al. (2017) BDNFVal66met polymorphism: a potential bridge between depression and thrombosis. Eur Heart J 38:1426-1435
Dincheva, Iva; Yang, Jianmin; Li, Anfei et al. (2017) Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice. Am J Psychiatry 174:1203-1213
Marrocco, Jordan; Petty, Gordon H; Ríos, Mariel B et al. (2017) A sexually dimorphic pre-stressed translational signature in CA3 pyramidal neurons of BDNF Val66Met mice. Nat Commun 8:808
Ieraci, Alessandro; Madaio, Alessandro I; Mallei, Alessandra et al. (2016) Brain-Derived Neurotrophic Factor Val66Met Human Polymorphism Impairs the Beneficial Exercise-Induced Neurobiological Changes in Mice. Neuropsychopharmacology 41:3070-3079
Hill, Matthew N; Lee, Francis S (2016) Endocannabinoids and Stress Resilience: Is Deficiency Sufficient to Promote Vulnerability? Biol Psychiatry 79:792-793

Showing the most recent 10 out of 57 publications