RESEARCH & FACULTY

Donald Ingram, Ph.D. Professor Department/Laboratory: Nutritional Neuroscience and Aging Comparative Metabolic and Behavioral Core
Phone: (225) 763-2594	Fax: (225) 763-0261
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EDUCATION

Louisiana State University, Baton Rouge, LA B.A. 1966-1970 Psychology
University of Georgia, Athens, GA M.S. 1974-1977 Psychology
University of Georgia, Athens, GA Ph.D. 1977-1978 Psych & Gerontology
The Jackson Laboratory, Bar Harbor, ME Post-doc 1978-1980 Behavior Genetics
National Institute on Aging, NIH, Baltimore, MD Staff Fellow 1980-1984 Neurobiology of Aging

Position prior to joining PBRC:

Chief, Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD

RESEARCH INTERESTS

Dr. Ingram’s research has focused on nutritional and pharmacological interventions designed to slow the rate of aging and thus reduce the risk of age-related disease and functional decline. The major area of investigation involves in vivo rodent models and in vitro cellular models to identify protective mechanisms invoked by calorie restriction. Long-term calorie restriction has been shown in a wide variety of species to increase lifespan, decrease age-related disease, improve stress responses, and attenuate age-related functional impairments. As a major new research area, his lab is investigating the development of calorie restriction mimetics. The objective is to identify compounds that mimic effects of calorie restriction by targeting metabolic and stress response pathways affected, but without actually restricting caloric intake. Other major lab activities involve developing and conducting behavioral assays of aging in rodents with focus on motor and memory performance. The objective is to identify mechanisms of age-related decline in motor and memory performance. As a primary objective of this research, investigations are directed toward preclinical development of pharmacological, hormonal, genetic, and nutritional interventions that improve behavioral function. To identify age-related structural changes in the brain and alterations produced through various interventions, morphometric analysis using unbiased stereology is applied.

SELECTED PUBLICATIONS

Roth GS, Mattison JA, Ottinger MA, Chachich M, Lane MA, Ingram DK. Aging in
rhesus monkeys: Relevance to human health interventions, Science, 305: 1423-1426, 2004.

Mamczarz J, Duffy K, Bowker J, Hagepanos A, Ingram D. Enhancement of amphetamine-induced locomotor response in rats on different regimens of diet restriction and 2-deoxyglucose treatment, Neuroscience, 131: 451-461, 2005.

Mattison J, Black A, Huck, J.,Moscrip T, Handy A,Tilmont T, Roth GS, Lane, MA, Ingram DK. Age-related decline in caloric intake and motivation for food in rhesus monkeys. Neurobiology of Aging, 26: 1117-1127, 2005.

Devan BD, Bowker JL, Bharati IS, Duffy KB, Nelson CM, Spangler EL, Ingram DK. The phosphodiesterase inhibitor sildenafil citrate attenuates the learning impairment in rats induced by nitric oxide synthase inhibition, Psychopharmacology, 183, 439-445, 2006.

Ingram DK, Zhu M, Mamczarz J, Zou S, Lane, MA, Roth GS, de Cabo R. Calorie restriction mimetics: An emerging research field. Aging Cell, 5: 97-108, 2006.

Lee GD, Longo D, Wang Y, Rifkind JM, Abdul-Raman L, Mamczarz JA, Duffy KB, BowkerJL, Spangler EL, Taub DD, Furukawa K, Mattson MP, Ingram DK. Cancer chemotherapy transiently improves cognitive function and synaptic plasticity in rats. Clinical Cancer Research. 12:198-205, 2006.

Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Vinayakuma VP, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy R, Fishbein KW, Spencer RG, Lakatta EG, LeCourteur D, Shaw RJ, Navas P, Puigerver P, Ingram DK, deCabo R, Sinclair DA. Resveratrol improves health and increases survival of mice on a high-calorie diet. Nature, 444: 337-342, 2006.

Devan, BD, Pistell, PJ, Daffin LW Jr, Nelson CM, Duffy KB, Bowker JL, Bharati IS, Sierra-Mercado D, Spangler EL, Ingram DK. Sildenafil citrate attenuates a complex maze impairment induced by intracerebroventricular infusion of the NOS inhibitor N?-nitro-L-arginine methyl ester. European Journal of Pharmacology, 563:134-140, 2007.

Duffy KB, Spangler EL, Devan BD, Guo Z, Bowker JL, Janas AM, Hagepanos A, Minor RK, DeCabo R, Mouton PR, Shukitt-Hale BA, Joseph JA, Ingram DK. A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiology of Aging, 29: 1680-1689, 2007.

Ingram DK, Young J, Mattison JA. Calorie restriction in nonhuman primates: Assessing effects on brain and behavioral aging. Neuroscience, 145: 1359-1364, 2007.

Mattison JA, Roth GS, Lane MA, Ingram DK. Calorie restriction in aging nonhuman primates. In: Mobbs, C.V., Yen, K., Hof, P.R., (Eds): Mechanisms of Caloric Restriction in Aging. Interdisciplinary Topics in Gerontology Basel, Karger, 2007, vol 35, pp. 137-158.

O'Neil JN, Mouton PR, Tizabi Y, Ottinger MA, Lei DL, Ingram DK, Manaye KF. Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice. Journal of Chemical Neuroanatomy 34:102-107, 2007.

Pistell PJ, Daffin LW, Jr, Nelson CM, Duffy KB, Bowker JL, Spangler EL, Ingram DK, Devan BD. Combined administration of subthreshold doses of the nitric oxide inhibitor, nitro-L-arginine, and muscarinic receptor antagonist, scopolamine, impairs complex maze learning in rats. Behavioural Pharmacology.18: 801-805, 2007.

Stote KS, Baer DJ, Spears K, Paul DR, Harris GK, Rumpler WV, Strycular P, Najjar SS, Ferrucci L, Ingram DK, Longo DL, Mattson MP. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal weight middle-aged men and women. American Journal of Clinical Nutrition 85:981-988, 2007.

Minor RK, Villarreal J, McGraw M, Percival SS, Ingram DK, de Cabo R. Calorie restriction alters physical performance but not cognition in two models of altered neuroendocrine signaling. Behavioural Brain Research, 189:202-211, 2008.

Pistell PJ, Zhu M, Ingram DK. Acquisition of conditioned taste aversion is impaired in the APP/PS1 mouse model of Alzheimer’s disease. Neuroscience, 152:594-600, 2008.

Pearson KJ, Lewis KN, Price NL, Chang JW, Perez E, Cascajo MV, Tamashiro KL, Poosala S, Csiszar A, Ungvari Z, Kensler TW, Yamamoto M, Egan JM, Longo DL, Ingram DK, Navas P, de Cabo R. Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction. Proceedings of the National Academy of Sciences, USA, 105:2325-2330, 2008.

Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R. Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. Cell Metabolism. 8: 157-168, 2008.

Shukitt-Hale B, Lau FC, Carey AN, Galli RL, Spangler EL, Ingram DK, Joseph JA. Blueberry polyphenols attenuate kainic acid induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutritional Neuroscience 11: 172-182, 2008.

Umegaki H, Roth GS, Ingram DK. Aging of the striatum: Mechanisms and interventions, Journal of the American Aging Association, 30: 251-261, 2008.

Pistell PJ, Nelson CM, Miller MG, Ingram DK, Devan BD. Striatal lesions interfere with acquisition of a complex maze task in rats. Behavioural Brain Research, 197: 138-143, 2009.
Ahmet I, Spangler E, Shukitt-Hale B, Juhaszova M, Sollott SJ, Joseph JA, Ingram DK, Talan M. Blueberry-enriched diet protects rat heart from ischemic damage. PLoS One 4:e5954, 2009.

White CL, Pistell PJ, Purpera MN, Gupta S, Fernandez-Kim SO, Hise TL, Keller JN, Ingram DK, Morrison CD, Bruce-Keller AJ. Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: Contributions of maternal diet. Neurobiol Dis 35:3-13, 2009.
Mouton PR, Chachich ME, Quigley C, Spangler E, Ingram DK. Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice. Neurosci Lett 464:184-7, 2009.

Ahmet I, Spangler E, Shukitt-Hale B, Joseph JA, Ingram DK, Talan M. Survival and cardioprotective benefits of long-term blueberry enriched diet in dilated cardiomyopathy following myocardial infarction in rats. PLoS One 4:e7975, 2009.

Zou S, Carey JR, Liedo P, Ingram DK, Yu B, Ghaedian R. Prolongevity effects of an oregano and cranberry extract are diet-dependent in the Mexican fruit fly (Anastrepha ludens). J Gerontol A Biol Sci Med Sci 65:41-50, 2010.

Pistell PJ, Ingram DK. Development of a water-escape motivated version of the Stone T-maze for mice. Neuroscience 166:61-72, 2010.

Pistell PJ, Morrison CD, Gupta S, Knight AG, Keller JN, Ingram DK, Bruce-Keller AJ. Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol 219: 25-32, 2010.

Bruce-Keller AJ, White CL, Gupta S, Knight AG, Pistell PJ, Ingram DK, Morrison CD, Keller JN. NOX activity in brain aging: Exacerbation by high fat diet. Free Radic Biol Med 49(1):22-30, 2010.

Smith DL Jr, Elam CF Jr, Mattison JA, Lane MA, Roth GS, Ingram DK, Allison DB. Metformin supplementation and life span in Fischer-344 rats. J Gerontol A Biol Sci Med Sci 65:468-74, 2010.

Morrison CD, Pistell PJ, Ingram DK, Johnson WD, Liu Y, Fernandez-Kim SO, White CL, Purpera MN, Uranga RM, Bruce-Keller AJ, Keller JN High Fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: Implications for decreased Nrf2 signaling. J Neurochem. 114:1471-14159, 2010.

Pistell, P.J., S. Gupta, A. G. Knight, M. Domingue, R.M. Uranga, D.K. Ingram, I. Kheterpal, C. Ruiz, J.N. Keller and A.J. Bruce-Keller (2010) Metabolic and neurologic consequences of chronic liponavir/ritonavir administration to C57BL/6 mice. Antivir ^ top