The broad aim of these studies is to further the understanding of how aging affects neuroplasticity in the brain. While initial studies suggested that neocortical neurons are lost with age, it is now clear that minimal neuron loss accompanies normal aging. A working hypothesis is that morphomolecular plasticity is lost within otherwise intact neocortical circuits, and these alterations drive age-related cognitive decline. However, surprisingly little is known about age-related synaptic changes in the aging rat neocortex, and direct evidence for reductions in adaptive plasticity in the aged brain is currently lacking. I propose to use stress as a model of adaptive neocortical plasticity;in young animals, I hypothesize that stress-induced neocortical neuron atrophy and subsequent behavioral impairments are reversible with recovery. However, I hypothesize that the ability to reversibly remodel neocortical neuronal dendrites and synapses will be diminished in the aged brain, and this will be reflected in diminished behavioral performance. An additional focus will be examining alterations of neocortical neuromodulatory receptor systems, which have also been posited as a mechanism for stress- and age-related cognitive decline. These studies will provide a solid neurobiological framework for future therapeutic interventions that aim to restore neuronal plasticity in the aging brain. As the mission of the NIA is to improve and aid in the quality of life of the elderly, an understanding of the fundamental biological mechanisms behind alterations in the aging brain is essential. To test these hypotheses, I will use a behavioral task that is well-characterized and previously shown to be both dependant on specific neocortical regions and sensitive to stress. For neurobiological investigations, I will use single cell dye-filling techniques and unbiased stereological electron microscope techniques that have proven highly successful in previous experiments in our laboratory. The use of these techniques is important because a large emphasis will be placed on alterations of dendritic spine morphological and receptor expression profiles with aging.

Public Health Relevance

The fastest growing segment of our population is the elderly, and despite much effort, a solid understanding of exactly how aging affects the brain is lacking. The research proposed in this application will use behavioral and cellular measures to study how the aged brain responds differentially to challenge than the young brain. These experiments will set the stage for therapeutic studies that will aim to lessen the deleterious impact of the aging process on brain function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AG034794-03
Application #
8121395
Study Section
Special Emphasis Panel (ZRG1-F01-W (20))
Program Officer
Wise, Bradley C
Project Start
2009-09-25
Project End
2012-02-17
Budget Start
2011-09-25
Budget End
2012-02-17
Support Year
3
Fiscal Year
2011
Total Cost
$29,148
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Neurosciences
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Bloss, Erik B; Puri, Rishi; Yuk, Frank et al. (2013) Morphological and molecular changes in aging rat prelimbic prefrontal cortical synapses. Neurobiol Aging 34:200-10
Ohm, Daniel T; Bloss, Erik B; Janssen, William G et al. (2012) Clinically relevant hormone treatments fail to induce spinogenesis in prefrontal cortex of aged female rhesus monkeys. J Neurosci 32:11700-5
Karatsoreos, Ilia N; Bhagat, Sarah; Bloss, Erik B et al. (2011) Disruption of circadian clocks has ramifications for metabolism, brain, and behavior. Proc Natl Acad Sci U S A 108:1657-62
Bloss, Erik B; Janssen, William G; Ohm, Daniel T et al. (2011) Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex. J Neurosci 31:7831-9
Bloss, Erik B; Janssen, William G; McEwen, Bruce S et al. (2010) Interactive effects of stress and aging on structural plasticity in the prefrontal cortex. J Neurosci 30:6726-31