Role of Specific Growth Factors in Aging

Bradshaw, Ralph A.

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 #: 5P01AG000538-13
• Application #: 3813668
• Support Year: 13
• Fiscal Year: 1989

Institution

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

Publications

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 :

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; Cotman, Carl W (2017) On the road towards the global analysis of human synapses. Neural Regen Res 12:1586-1589

Chen, E Y; Chu, S; Gov, L et al. (2017) CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic co-glycolic acid) microparticles and films. J Mater Chem B 5:1574-1584

Snigdha, Shikha; Yassa, Michael A; deRivera, Christina et al. (2017) Pattern separation and goal-directed behavior in the aged canine. Learn Mem 24:123-131

Hernandez, Michael X; Namiranian, Pouya; Nguyen, Eric et al. (2017) C5a Increases the Injury to Primary Neurons Elicited by Fibrillar Amyloid Beta. ASN Neuro 9:1759091416687871

Hatami, Asa; Monjazeb, Sanaz; Milton, Saskia et al. (2017) Familial Alzheimer's Disease Mutations within the Amyloid Precursor Protein Alter the Aggregation and Conformation of the Amyloid-? Peptide. J Biol Chem 292:3172-3185