We have conducted experiments using Octopus vulgaris as an experimental animal that have given some new insights into the nature of the processes that take place in a learning neuropil during the learning process that might be applicable to the human brain. In particular we have studied a neuropil in which we know that tactile learning is taking place during a training period and have found two related things that suggest experiments that we propose to do with human brain material that may relate to the learning and memory deficiencies of Alzheimer disease. We have postulated that a primary step in learning is rearrangements of neurites in the participating neuropils that is a preamble to the formation of new synapses. If this is so then one would expect to see some signs of growth cone activity and one of the most prominent of these is the extension of filopodia. It follows that injection into the neuropil of cytochalasin B should block learning because this drug leads to depolymerization of actin which must be polymerized for filopodial extension. Further the drug should not affect existing memories. Our experiments show that both these conditions are met in Octopus, supporting our general hypothesis. We have also conducted a preliminary morphometric study of the same neuropil during training and found that as the animal begins to learn there is an increase in the volume frequency of filopodia. On the basis of these findings it is reasonable to ask whether or not there is evidence in human brain neuropils of filopodial activity that may be involved in learning and memory. We therefore plan to study human brain material by electron microscopy to answer this question. In particular we plan to collect specimens containing neuropils from regions of the human brain that might be involved in learning and study them by electron microscopy looking specifically for filopodia. We shall concentrate on the hippocampus but shall take specimens from frontal, parietal, temporal and occipital lobe cortex. We shall study them by transmission and scanning electron microscopy techniques.
Our aim i s to determine whether or not the brains of Alzheimer disease patients differ than normal brains in regard to the above structural features and in any case to describe the Alzheimer's and normal brains with respect to these features.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
2P50AG005128-07
Application #
3809136
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Duke University
Department
Type
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Petyuk, Vladislav A; Chang, Rui; Ramirez-Restrepo, Manuel et al. (2018) The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target. Brain 141:2721-2739
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
Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384
Karch, Celeste M; Ezerskiy, Lubov A; Bertelsen, Sarah et al. (2016) Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One 11:e0148717
Mez, Jesse; Mukherjee, Shubhabrata; Thornton, Timothy et al. (2016) The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable. Neurobiol Aging 41:115-121
Ridge, Perry G; Hoyt, Kaitlyn B; Boehme, Kevin et al. (2016) Assessment of the genetic variance of late-onset Alzheimer's disease. Neurobiol Aging 41:200.e13-200.e20
Hohman, Timothy J; Bush, William S; Jiang, Lan et al. (2016) Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium. Neurobiol Aging 38:141-150
Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M et al. (2016) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21:108-17
Hohman, Timothy J; Cooke-Bailey, Jessica N; Reitz, Christiane et al. (2016) Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk. Alzheimers Dement 12:233-43
Ghani, Mahdi; Reitz, Christiane; Cheng, Rong et al. (2015) Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals. JAMA Neurol 72:1313-23

Showing the most recent 10 out of 97 publications