Date(s) - 04/08/2013
The extent and cost of care required for our burgeoning elderly population will greatly depend upon their level of cognitive ability. Chronological age is not a direct predictor of this cognitive decline, which can vary in degree of impairment without any obvious pathology, such as Alzheimer’s disease. Instead, cognitive decline may be due to dysregulated expression of pro- and anti-inflammatory cytokines, among other proteins. Senescent rats can be characterized as memory-unimpaired or memory-impaired using behavioral tasks such as the water maze. Interestingly, these memory impairments begin to appear in middle age, when inflammatory gene expression is also increased. The protein compliment of these gene products could comprise a unique biomarker array to predict and/or diagnose age-related cognitive decline. Young (4-8 mo), middle-aged (12 mo) and aged (18-22 mo) Fisher 344 rats were behaviorally characterized, hippocampal neurogenesis was immunohistochemically evaluated using light and confocal microscopy, potential biomarkers were identified in the blood serum and brain using Bio-Plex technology and correlation analyses were used to reveal the relationships between these measures and create cytokine pathway clusters. The data presented in this dissertation demonstrate 1) hippocampal neurogenesis, correlates with learning and memory task performance in aged rats, 2) memory-impaired rats have a distinct inflammatory cytokine profile, 3) inflammatory cytokine expression correlates with hippocampal neurogenesis and learning/memory and is altered by physical activity and 4) simple lifestyle changes, including physical environmental enrichment and physical exercise, can also alter cytokine expression and preserve hippocampal plasticity and integrity across age. Identification of biomarkers capable of predicting cognitive impairment may lead to the engineering of an assay panel that can be used to monitor blood samples of the aging human population.