A major problem in the study of animal models of neurodegenerative disease is the lack of an unambiguous marker to identify dying neurons. A new method, the terminal transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique involves the end labeling of fragmented DNA associated with dying cells with biotinylated nucleotides, after which cells are visualized via avidin-conjugated peroxidase. The method has been used successfully to label cells undergoing programmed death in the digestive, lymphatic, and reproductive systems and skin. TUNEL has not been applied to studies of cell death in the nervous system, and in this Pilot, we propose a series of experiments designed to investigate the validity and usefulness of this technique as a tool to enhance our understanding of neuronal cell death. Initially, we will validate the selectivity and specificity of the technique on tissues from the spinal cord of rats at embryonic day 16, a time point at which naturally occurring motor neuron death has been reported. Subsequently, we will examine three animal models of retrograde neuronal degeneration that are well established in our laboratory, one involving neonatal and the other two involving adult neurons. The studies described in this Pilot will allow us to determine the usefulness of TUNEL in identifying degenerating neurons. This strategy will then be used to investigate these issues in other models, including transgenic mice in our Alzheimer's Disease Research Center (ADRC), and eventually, to focus this approach on processes that lead to death of neurons in the human brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005146-14
Application #
5204510
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1996
Total Cost
Indirect Cost
van Bergen, Jiri M G; Li, Xu; Quevenco, Frances C et al. (2018) Low cortical iron and high entorhinal cortex volume promote cognitive functioning in the oldest-old. Neurobiol Aging 64:68-75
Brent, Robert J (2018) Estimating the monetary benefits of medicare eligibility for reducing the symptoms of dementia. Appl Econ 50:6327-6340
Kim, Sangjune; Yun, Seung Pil; Lee, Saebom et al. (2018) GBA1 deficiency negatively affects physiological ?-synuclein tetramers and related multimers. Proc Natl Acad Sci U S A 115:798-803
Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872
Burke, Shanna L; Maramaldi, Peter; Cadet, Tamara et al. (2018) Decreasing hazards of Alzheimer's disease with the use of antidepressants: mitigating the risk of depression and apolipoprotein E. Int J Geriatr Psychiatry 33:200-211
Hohman, Timothy J; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA Neurol 75:989-998
Kales, Helen C; Gitlin, Laura N; Stanislawski, Barbara et al. (2018) Effect of the WeCareAdvisor™ on family caregiver outcomes in dementia: a pilot randomized controlled trial. BMC Geriatr 18:113
Kageyama, Yusuke; Saito, Atsushi; Pletnikova, Olga et al. (2018) Amyloid ? toxic conformer has dynamic localization in the human inferior parietal cortex in absence of amyloid plaques. Sci Rep 8:16895
Reagh, Zachariah M; Noche, Jessica A; Tustison, Nicholas J et al. (2018) Functional Imbalance of Anterolateral Entorhinal Cortex and Hippocampal Dentate/CA3 Underlies Age-Related Object Pattern Separation Deficits. Neuron 97:1187-1198.e4
Qian, Winnie; Fischer, Corinne E; Schweizer, Tom A et al. (2018) Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease. Curr Alzheimer Res 15:187-194

Showing the most recent 10 out of 830 publications