Abstract

The project is divided into four main specific aims and sections. These are: (1) Experiments to determine whether nerve growth factor (NGF) or NGF-like (i.e. immunologically cross-reactive with mouse NGF or derived from an mRNA that bears sequence homology to that of mouse NGF) molecules are present in the brain. This will be done by Northern- and Western-blot analyses using a cDNA probe for NGF and antibody to NGF. If such material is detected, it will be analyzed by amino acid sequencing. Material detected by Northerns would be cloned by one of several alternative techniques. (2) Levels of mRNA for NGF or NGF-like molecules will be measured (using appropriate cDNA probes) in various regions of postmortem human brains. Such findings will be correlated with any known pathologies of the material. Animal models will also be studied for changes in mRNA levels for NGF or NGF-like molecules in various brain regions as a function of aging and possible pathology. (3) cDNA and antibody reagents will be derived for pituitary fibroblast growth factor (FGF). These tools will be used to study protein and mRNA levels for FGF in various brain regions during aging and in pathological conditions (especially Alzheimer disease). (4) Guidance will be provided for the purification and characterization of the ciliary neuron neuronotrophic factor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG000538-11
Application #
3821493
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California Irvine
Department
Type
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Sosna, Justyna; Philipp, Stephan; Albay 3rd, Ricardo et al. (2018) Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer's disease. Mol Neurodegener 13:11
Tong, Liqi; Prieto, G Aleph; Cotman, Carl W (2018) IL-1? suppresses cLTP-induced surface expression of GluA1 and actin polymerization via ceramide-mediated Src activation. J Neuroinflammation 15:127
Hainsworth, A H; Lee, S; Foot, P et al. (2018) Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). Neuropathol Appl Neurobiol 44:417-426
Krotee, Pascal; Griner, Sarah L; Sawaya, Michael R et al. (2018) Common fibrillar spines of amyloid-? and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors. J Biol Chem 293:2888-2902
Prieto, G Aleph; Tong, Liqi; Smith, Erica D et al. (2018) TNF? and IL-1? but not IL-18 Suppresses Hippocampal Long-Term Potentiation Directly at the Synapse. Neurochem Res :
Carlos, Anthony J; Tong, Liqi; Prieto, G Aleph et al. (2017) IL-1? impairs retrograde flow of BDNF signaling by attenuating endosome trafficking. J Neuroinflammation 14:29
Fonseca, Maria I; Chu, Shu-Hui; Hernandez, Michael X et al. (2017) Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain. J Neuroinflammation 14:48
Abud, Edsel M; Ramirez, Ricardo N; Martinez, Eric S et al. (2017) iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases. Neuron 94:278-293.e9
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738
Gonzalez, Bianca; Abud, Edsel M; Abud, Abigail M et al. (2017) Tau Spread, Apolipoprotein E, Inflammation, and More: Rapidly Evolving Basic Science in Alzheimer Disease. Neurol Clin 35:175-190

Showing the most recent 10 out of 281 publications