The research proposed here will make quantitative measures of dendrites in descriptive study in aging human ventral cochlear nucleus and in experimental study in rodent entorhinal cortex. These studies are designed to test hypotheses regarding the regulation of dendritic extent in aging brain by events in the local extra-cellular environment: that loss of input promotes dendritic regression, and the death of neurons promotes dendritic proliferation in surviving, neighboring neurons. The human ventral cochlear nucleus presents a model of loss of input from neurons in the spiral ganglion. In the rodent entorhinal cortex death of a selected sub-population of neurons will be produced by suicide transport from the molecular layer of the dentate gyrus to layer II stellate neurons. Dendritic trees of surviving, neighboring superficial pyramidal neurons and layer II stellates (the same class killed) will be quantified. Measures from these experimental brains will be compared to control brains from same age animals to determine whether neuron death produced experimentally promotes dendritic proliferation in surviving neighboring neurons, and whether any effect seen is restricted to the same class of neuron that was killed. Details of the distribution of dendritic trees in entorhinal cortex will be exploited to distinguish between two classes of possible mechanisms: reduced dendritic competition for afferent supply or, elaboration of a neuronotrophic factor. Also in rodent entorhinal cortex we will determine whether the generally accepted dendritic regression produced by lesions of afferent supply becomes more severe in aged animals. This will be explored by making lesions in the nucleus reuniens thalami (a major input to entorhinal cortex) in animals at several ages and determining the effect of this partial deafferentation on dendritic trees as a function of age.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG001121-09
Application #
3114160
Study Section
Neurology A Study Section (NEUA)
Project Start
1978-07-01
Project End
1989-03-31
Budget Start
1986-07-01
Budget End
1989-03-31
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Callahan, Linda M; Vaules, William A; Coleman, Paul D (2002) Progressive reduction of synaptophysin message in single neurons in Alzheimer disease. J Neuropathol Exp Neurol 61:384-95
Chang, J W; Young, D A; Coleman, P D et al. (2001) Two-dimensional gel analysis of secreted proteins induced by interleukin-1 beta in rat astrocytes. Neurochem Int 39:349-59
Callahan, L M; Vaules, W A; Coleman, P D (1999) Quantitative decrease in synaptophysin message expression and increase in cathepsin D message expression in Alzheimer disease neurons containing neurofibrillary tangles. J Neuropathol Exp Neurol 58:275-87
Yao, P J; Coleman, P D (1998) Reduction of O-linked N-acetylglucosamine-modified assembly protein-3 in Alzheimer's disease. J Neurosci 18:2399-411
Combs, C K; Coleman, P D; O'Banion, M K (1998) Developmental regulation and PKC dependence of Alzheimer's-type tau phosphorylations in cultured fetal rat hippocampal neurons. Brain Res Dev Brain Res 107:143-58
Yao, P J; Coleman, P D (1998) Reduced O-glycosylated clathrin assembly protein AP180: implication for synaptic vesicle recycling dysfunction in Alzheimer's disease. Neurosci Lett 252:33-6
Cheetham, J E; Coleman, P D; Chow, N (1997) Isolation of single immunohistochemically identified whole neuronal cell bodies from post-mortem human brain for simultaneous analysis of multiple gene expression. J Neurosci Methods 77:43-8
Cheetham, J E; Martzen, M R; Kazee, A M et al. (1996) Gap-43 message levels in anterior cerebellum in Alzheimer's disease. Brain Res Mol Brain Res 36:145-51
O'Banion, M K; Miller, J C; Chang, J W et al. (1996) Interleukin-1 beta induces prostaglandin G/H synthase-2 (cyclooxygenase-2) in primary murine astrocyte cultures. J Neurochem 66:2532-40
Callahan, L M; Coleman, P D (1995) Neurons bearing neurofibrillary tangles are responsible for selected synaptic deficits in Alzheimer's disease. Neurobiol Aging 16:311-4

Showing the most recent 10 out of 28 publications