EARLY EVENTS IN ALZHEIMER PATHOGENESIS

Summary

Principal Investigator: SUE TILTON GRIFFIN
Abstract: This Program has provided compelling evidence for a self amplifying cycle of interactions between neurons and glia, mediated largely by neuroinflammatory cytokines acting as drivers of Alzheimer's disease (AD) pathogenesis;chief among these is interleukin-1 (IL-1). We have focused on the entry points into this cycle, which is to say the early events in a given neuron's circuit of interactions with its local environs. Recent examinations of human tissue and of a newly acquired transgenic Alzheimer model indicate that pathology of the Alzheimer type is initially associated with neuronal elevation of apolipoprotein E (ApoE) and -amyloid precursor protein (APP). Empirical studies in cell culture suggest that the APP/ApoE response in tissue is due to a causal relationship in which APP expression is dependent on co-expression of ApoE, with ApoE e3 more efficacious than ApoE e4, and is modulated by IL-1. Neuronal APP elevation is accompanied by secretion of APP fragments, which activate microglia and cause glutamate release. Together, this suggests that a glutamate-ApoE-APP axis is initialized in the early neuronal responses to adverse stimuli and neuroinflammation. With these results, we were surprised to find that i) APP expression declines in neuronal somata as one approaches mature A plaques, either temporally or spatially;and ii) glial activation persists in Alzheimer brain in the presence or following "clearance" of A plaques. Together, these data inspire a hypothesis that unifies the current renewal of this Program: The typical acute-phase response of neurons to adverse stimuli is to elevate ApoE and APP expression via a coordinated, causal relationship between ApoE and APP expression that becomes uncoupled in AD pathogenesis, leaving neurons with insufficient APP and a propensity to make inappropriate cellular responses and to succumb to the excitotoxic stress perpetrated by "classical" activation of microglia. Human tissue and model systems will be used in Project 1 to identify and elucidate the basic elements of the glutamate-ApoE-APP axis, and the role of IL-1 in its failure in AD. Project 2 will identify, in two unique populations, common pathways for microglial activation and cytokine release and the degree to which this activation is reflected in mRNA and protein expression profiles. Project 3 will investigate key aspects of microglial activation related to oxidative production of glutamate and the differential modulation of this activation by IL-1a gene polymorphisms. Three cores provide administrative coordination (Core A), tissue banking and processing (Core B), and molecular/biochemical sample analyses (Core C) for these studies. The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD.
Funding Period: 1997-08-01 - 2015-03-31
more information: NIH RePORT

Top Publications

  1. pmc PKCδ/midkine pathway drives hypoxia-induced proliferation and differentiation of human lung epithelial cells
    Hanying Zhang
    Department of Animal Sciences, University of Wyoming, Laramie, Wyoming
    Am J Physiol Cell Physiol 306:C648-58. 2014
  2. pmc Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade
    W Michael Zawada
    Donald W, Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Neuroinflammation 8:129. 2011
  3. pmc Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy
    Haiyan Jiang
    School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, 270 Xueyuan Road, Wenzhou, Zhejiang 325003, P R China
    J Neuroinflammation 8:119. 2011
  4. ncbi Striatal Aβ peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes
    M E Kalaitzakis
    Neuropathology Unit, Centre for Neuroscience, Division of Experimental Medicine, Department of Medicine, Imperial College London, Charing Cross Campus, St Dunstan s Road, London, UK
    Neurobiol Dis 41:377-84. 2011
  5. ncbi Capillary cerebral amyloid angiopathy identifies a distinct APOE epsilon4-associated subtype of sporadic Alzheimer's disease
    Dietmar Rudolf Thal
    Institute of Pathology, University of Ulm, Albert Einstein Allee 11, Ulm, Germany
    Acta Neuropathol 120:169-83. 2010
  6. pmc Genetic loss of D-amino acid oxidase activity reverses schizophrenia-like phenotypes in mice
    V Labrie
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
    Genes Brain Behav 9:11-25. 2010
  7. ncbi Neuropathology and the neuroinflammation idea
    Robert E Mrak
    Department of Pathology, 2280 Dowling Hall, University of Toledo Health Science Campus MS 1090, 3000 Arlington Avenue, Toledo, OH 43614, USA
    J Alzheimers Dis 18:473-81. 2009
  8. ncbi Clinical correlates of pathology in the claustrum in Parkinson's disease and dementia with Lewy bodies
    M E Kalaitzakis
    Department of Clinical Neuroscience, Neuropathology Unit, Division of Neuroscience and Mental Health, Imperial College Healthcare NHS Trust, London, UK
    Neurosci Lett 461:12-5. 2009
  9. pmc Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model
    Viviane Labrie
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Hum Mol Genet 18:3227-43. 2009
  10. pmc Unique aspects of transcriptional regulation in neurons--nuances in NFkappaB and Sp1-related factors
    Xianrong R Mao
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Neuroinflammation 6:16. 2009

Research Grants

  1. Alerations of Sleep and Circadian Timing in Aging
    Eve Van Cauter; Fiscal Year: 2013

Detail Information

Publications51

  1. pmc PKCδ/midkine pathway drives hypoxia-induced proliferation and differentiation of human lung epithelial cells
    Hanying Zhang
    Department of Animal Sciences, University of Wyoming, Laramie, Wyoming
    Am J Physiol Cell Physiol 306:C648-58. 2014
    ..Manipulation of PKCδ and MK activity in epithelial cells might be beneficial for the treatment of hypoxia-mediated lung diseases. ..
  2. pmc Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade
    W Michael Zawada
    Donald W, Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Neuroinflammation 8:129. 2011
    ....
  3. pmc Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy
    Haiyan Jiang
    School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, 270 Xueyuan Road, Wenzhou, Zhejiang 325003, P R China
    J Neuroinflammation 8:119. 2011
    ..We tested possibility that SR and its product, D-serine, were altered in a rat model of DR...
  4. ncbi Striatal Aβ peptide deposition mirrors dementia and differentiates DLB and PDD from other parkinsonian syndromes
    M E Kalaitzakis
    Neuropathology Unit, Centre for Neuroscience, Division of Experimental Medicine, Department of Medicine, Imperial College London, Charing Cross Campus, St Dunstan s Road, London, UK
    Neurobiol Dis 41:377-84. 2011
    ..More detailed examination of the morphology of the Aβ pathology suggests that it is the presence of cored amyloid plaques in DLB, but not PDD, that underlies the differences seen in PET imaging...
  5. ncbi Capillary cerebral amyloid angiopathy identifies a distinct APOE epsilon4-associated subtype of sporadic Alzheimer's disease
    Dietmar Rudolf Thal
    Institute of Pathology, University of Ulm, Albert Einstein Allee 11, Ulm, Germany
    Acta Neuropathol 120:169-83. 2010
    ....
  6. pmc Genetic loss of D-amino acid oxidase activity reverses schizophrenia-like phenotypes in mice
    V Labrie
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
    Genes Brain Behav 9:11-25. 2010
    ..Diminished DAO activity and elevations in D-serine may serve as an effective therapeutic intervention for the treatment of psychiatric symptoms...
  7. ncbi Neuropathology and the neuroinflammation idea
    Robert E Mrak
    Department of Pathology, 2280 Dowling Hall, University of Toledo Health Science Campus MS 1090, 3000 Arlington Avenue, Toledo, OH 43614, USA
    J Alzheimers Dis 18:473-81. 2009
    ..Further observations have extended these ideas to alpha-synuclein-based diseases (Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy) as well as other neurodegenerative diseases and conditions...
  8. ncbi Clinical correlates of pathology in the claustrum in Parkinson's disease and dementia with Lewy bodies
    M E Kalaitzakis
    Department of Clinical Neuroscience, Neuropathology Unit, Division of Neuroscience and Mental Health, Imperial College Healthcare NHS Trust, London, UK
    Neurosci Lett 461:12-5. 2009
    ..13 and 0.1, respectively). We demonstrate that pathology in the claustrum, a region of largely obscure physiological function, strongly relates to the presence of dementia in Parkinson's disease and DLB...
  9. pmc Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model
    Viviane Labrie
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Hum Mol Genet 18:3227-43. 2009
    ..Furthermore, analysis of SRR genetic variants in humans identified a robust association with schizophrenia. This study demonstrates that aberrant Srr function and diminished d-serine may contribute to schizophrenia pathogenesis...
  10. pmc Unique aspects of transcriptional regulation in neurons--nuances in NFkappaB and Sp1-related factors
    Xianrong R Mao
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Neuroinflammation 6:16. 2009
    ..These findings and their implications for neuronal differentiation--as well as potential dedifferentiation during degenerative processes--are discussed here...
  11. pmc Paradoxical roles of serine racemase and D-serine in the G93A mSOD1 mouse model of amyotrophic lateral sclerosis
    Misty Thompson
    Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Neurochem 120:598-610. 2012
    ....
  12. pmc Roles of quaternary structure and cysteine residues in the activity of human serine racemase
    Wei Wang
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    BMC Biochem 12:63. 2011
    ..Regulation of SR activity is still poorly understood. As step toward developing reagents and methods for investigating SR in vitro, we analyzed structure-function relationships of a recombinant enzyme of human sequence...
  13. pmc Apolipoprotein E expression is elevated by interleukin 1 and other interleukin 1-induced factors
    Ling Liu
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Neuroinflammation 8:175. 2011
    ..These stressors include interleukin-1 (IL-1)-mediated neuroinflammation and glutamate-mediated excitotoxicity. Such circumstances are especially powerful when they transpire in the context of an APOE ε4 allele...
  14. pmc Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis
    Donna M Wilcock
    Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
    J Neuroinflammation 10:84. 2013
    ..the brains of fetuses, neonates, and children with DS opened the possibility that early events in Alzheimer pathogenesis were driven by cytokines...
  15. pmc Nox4-generated superoxide drives angiotensin II-induced neural stem cell proliferation
    Elena Topchiy
    Department of Behavioral Neuroscience, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Mail Code L470, Portland, OR 97239, USA
    Dev Neurosci 35:293-305. 2013
    ....
  16. ncbi Disturbed sleep in Parkinson's disease: anatomical and pathological correlates
    M E Kalaitzakis
    Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK
    Neuropathol Appl Neurobiol 39:644-53. 2013
    ..g. restless legs syndrome and rapid eye movement sleep behaviour disorder). However, the exact pathological basis of disturbed sleep remains as yet undefined...
  17. pmc Review: microglia in protein aggregation disorders: friend or foe?
    S M Gentleman
    Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK
    Neuropathol Appl Neurobiol 39:45-50. 2013
    ..A better understanding of their varied roles is essential if they are to be the target for novel therapeutic strategies...
  18. pmc A polymorphism in the upstream regulatory region of the interleukin-1α gene confers differential binding by transcription factors of the AP-1 family
    Andrea M Moerman-Herzog
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
    Life Sci 90:975-9. 2012
    ..We sought to determine the differential abilities of C- and T- containing versions of the -889 sequence to bind nuclear proteins from microglia...
  19. pmc Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience
    Orwa Aboud
    Donald W, Reynolds Department of Geriatrics, Reynolds Institute on Aging, 629 Jack Stephens Drive, Little Rock, AR 72205, USA
    BMC Med 10:35. 2012
    ....
  20. pmc Cross-linking of serine racemase dimer by reactive oxygen species and reactive nitrogen species
    Wei Wang
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
    J Neurosci Res 90:1218-29. 2012
    ..These findings suggest a compensatory feedback in which the consequences of neuroinflammation might dampen D-serine production to limit excitotoxic stimulation of NMDA receptors...
  21. pmc Muscle expression of genes associated with inflammation, growth, and remodeling is strongly correlated in older adults with resistance training outcomes
    Richard A Dennis
    Geriatric Reasearch, Education, and Clinical Center, Central Arkansas Veterans Healthcare System, No Little Rock, Arkansas 72114 1706, USA
    Physiol Genomics 38:169-75. 2009
    ..These genes hold promise as useful predictors of training outcomes that could be used to design more effective exercise regimens for maintaining muscle function in older adults...
  22. ncbi Alzheimer-type neuropathological changes in morbidly obese elderly individuals
    R E Mrak
    Department of Pathology, University of Toledo College of Medicine, 3000 Arlington Avenue, Toledo, OH 43614, USA
    Clin Neuropathol 28:40-5. 2009
    ..Middle age obesity increases risk for Alzheimer disease (AD). This study evaluated neuropathological changes in morbidly obese patients ranging in age from 21-70 years...
  23. pmc Genetic inactivation of D-amino acid oxidase enhances extinction and reversal learning in mice
    Viviane Labrie
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5, Canada
    Learn Mem 16:28-37. 2009
    ..The NMDAR glycine site and DAO may be promising therapeutic targets to improve cognitive flexibility and inhibitory learning in psychiatric disorders such as schizophrenia and anxiety syndromes...
  24. ncbi Association of the glutathione S-transferase omega-1 Ala140Asp polymorphism with cerebrovascular atherosclerosis and plaque-associated interleukin-1 alpha expression
    Heike Kolsch
    Stroke 38:2847-50. 2007
    ..The objective of this study is to address the question of whether common vessel disorders known to cause vascular dementia are modified in their severity by this polymorphism...
  25. ncbi Induction of serine racemase expression and D-serine release from microglia by secreted amyloid precursor protein (sAPP)
    Shengzhou Wu
    Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
    Curr Alzheimer Res 4:243-51. 2007
    ..D-serine may cooperate with glutamate to link neuroinflammation with excitotoxicity, suggesting a pathogenic mechanism applicable to neuronal death in AD and other neurodegenerative diseases...
  26. pmc Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation
    Steven W Barger
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
    J Neurochem 101:1205-13. 2007
    ..Indeed, some of the neuroprotective effects of antioxidants may be due to interference with these events rather than direct protection against neuronal oxidation...
  27. ncbi Alterations in presenilin 1 processing by amyloid-beta peptide in the rat retina
    Helena R Watts
    Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Campus, Fulham Palace Road, London, W6 8RF, UK
    Exp Brain Res 181:69-77. 2007
    ..These results suggest an A beta(1-42)-induced potentiation of a non-specific stress-related but inflammation-independent alteration of processing of PS1 in this in vivo model...
  28. pmc Glutamate receptor activation evokes calpain-mediated degradation of Sp3 and Sp4, the prominent Sp-family transcription factors in neurons
    Xianrong Mao
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
    J Neurochem 100:1300-14. 2007
    ..These data provide details of an impact of glutamate-receptor activation on molecular events connected to gene expression...
  29. ncbi Glycogen synthase kinase-3 in neurodegeneration and neuroprotection: lessons from lithium
    Saeed Yadranji Aghdam
    School of Biology, University of Tehran, Tehran 14155 6455, Iran
    Curr Alzheimer Res 4:21-31. 2007
    ....
  30. pmc Differential transcriptional control of the superoxide dismutase-2 kappaB element in neurons and astrocytes
    Xianrong Mao
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Biol Chem 281:35863-72. 2006
    ....
  31. ncbi Pioglitazone induces apoptosis of macrophages in human adipose tissue
    Angela M Bodles
    The Central Arkansas Veterans Healthcare System, and the Department of Medicine, Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Lipid Res 47:2080-8. 2006
    ....
  32. pmc Interleukin-1 mediates Alzheimer and Lewy body pathologies
    W Sue T Griffin
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Neuroinflammation 3:5. 2006
    ..Glial activation, with overexpression of interleukin-1 (IL-1) and other proinflammatory cytokines, has been increasingly implicated in the pathogenesis of both AD and PD...
  33. ncbi Inflammation and neurodegenerative diseases
    W Sue T Griffin
    Donald W Reynolds Department of Geriatrics, The University of Arkansas for Medical Sciences, and the Geriatric Research Education Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
    Am J Clin Nutr 83:470S-474S. 2006
    ..Over a period of years, this slow, smoldering inflammation in the brain destroys sufficient neurons to cause the clinical signs of Alzheimer disease...
  34. ncbi Common inflammatory mechanisms in Lewy body disease and Alzheimer disease
    Robert E Mrak
    Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Neuropathol Exp Neurol 66:683-6. 2007
    ..These neuroinflammatory processes may be a common link driving progression in both diseases and explaining the frequent overlap between the 2 diseases...
  35. ncbi The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson's disease: a critical analysis of alpha-synuclein staging
    M E Kalaitzakis
    University Department of Neuropathology, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Hospitals Trust, London, UK
    Neuropathol Appl Neurobiol 34:284-95. 2008
    ..However, the reliability of this stereotypical spread of alpha Syn pathology has been questioned. In addition, the comparative occurrence of alpha Syn pathology in the spinal cord and brain has not been closely studied...
  36. ncbi Glial expression of cannabinoid CB(2) receptors and fatty acid amide hydrolase are beta amyloid-linked events in Down's syndrome
    E Nunez
    Laboratorio de Apoyo a la Investigacion, Fundacion Hospital Alcorcon, 28922 Alcorcon, Madrid, Spain
    Neuroscience 151:104-10. 2008
    ..In addition, they confirm a striking differential pattern of distribution of FAAH and CB(2) receptors...
  37. ncbi Acute and chronic effects of intravitreally injected beta-amyloid on the neurotransmitter system in the retina
    Okezie I Aruoma
    Department of Pharmaceutical and Biomedical Sciences, Touro College of Pharmacy, New York, NY 10027, USA
    Toxicology 256:92-100. 2009
    ....
  38. pmc Relationships between expression of apolipoprotein E and beta-amyloid precursor protein are altered in proximity to Alzheimer beta-amyloid plaques: potential explanations from cell culture studies
    Steven W Barger
    Department of Geriatrics, Geriatric Research Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA
    J Neuropathol Exp Neurol 67:773-83. 2008
    ....
  39. ncbi Parenchymal and vascular Abeta-deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease
    Dietmar Rudolf Thal
    Institute of Pathology Laboratory of Neuropathology University of Ulm, Ulm, Germany
    J Cell Mol Med 12:1848-62. 2008
    ..Therefore, it seems to be necessary to protect the brain from Abeta-toxicity already in stages of the disease with minor neuron loss before the onset of cognitive symptoms...
  40. ncbi Dementia and visual hallucinations associated with limbic pathology in Parkinson's disease
    M E Kalaitzakis
    Department of Clinical Neuroscience, Neuropathology Unit, Division of Neuroscience and Mental Health, Imperial College Healthcare NHS Trust, London, UK
    Parkinsonism Relat Disord 15:196-204. 2009
    ..We conclude that alphaSyn in limbic regions is related to dementia in PD as well as to visual hallucinations when there is an underlying dementia...
  41. pmc Interactions between APP secretases and inflammatory mediators
    Magdalena Sastre
    Division of Neuroscience and Mental Health, Imperial College London, The Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    J Neuroinflammation 5:25. 2008
    ..In this review we will discuss some of these issues and the role of the secretases in inflammation, independent of their effect on Abeta formation...
  42. pmc Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletal muscle
    Mats Hidestrand
    College of Health Sciences, University of Kentucky, 900 S Limestone, CTW 105, Lexington, KY 40536 0200, USA
    J Gerontol A Biol Sci Med Sci 63:566-79. 2008
    ..Thus, with age, a subset of myoblasts takes on an altered phenotype, which is marked by high Sca-1 expression. These cells do not participate in muscle regeneration, and instead may contribute to muscle fibrosis in aged muscle...
  43. ncbi Cerebral amyloid angiopathy and its relationship to Alzheimer's disease
    Dietmar Rudolf Thal
    Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Albert Einstein Allee 7, 89081 Ulm, Germany
    Acta Neuropathol 115:599-609. 2008
    ..Thus, blood flow alterations with subsequent hypoperfusion induced by CAA-related capillary occlusion presumably point to a second mechanism in which A beta adversely affects the brain in AD in addition to its direct neurotoxic effects...
  44. ncbi Striatal beta-amyloid deposition in Parkinson disease with dementia
    Michail E Kalaitzakis
    University Department of Neuropathology, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Hospitals Trust, London, UK
    J Neuropathol Exp Neurol 67:155-61. 2008
    ..Striatal Abeta deposition was type-independent of Alzheimer disease changes in the cortex and was minimal in nondemented PD cases. We conclude that Abeta deposition in the striatum strongly correlates with dementia in PD...
  45. pmc Perispinal etanercept: potential as an Alzheimer therapeutic
    W Sue T Griffin
    Geriatric Research, Education and Clinical Center, Neurobiology, Physiology, and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Neuroinflammation 5:3. 2008
    ....
  46. ncbi Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise
    Richard A Dennis
    Central Arkansas Veterans Healthcare System, North Little Rock GRECC, 2200 Fort Roots Dr Bldg 170, 3J 157, North Little Rock, AR 72114 1706, USA
    Physiol Genomics 32:393-400. 2008
    ..Future studies must determine the functional importance of these gene expression changes to protein synthesis, satellite cell activity, and other processes that are directly involved in the mechanisms of muscle hypertrophy...
  47. ncbi Aging alters macrophage properties in human skeletal muscle both at rest and in response to acute resistance exercise
    Beata Przybyla
    Department of Geriatrics, University of Arkansas for Medical Sciences, 4301 West Markham 807, Little Rock, AR 72205, USA
    Exp Gerontol 41:320-7. 2006
    ..These findings suggest that aging results in a defective regulation of muscle macrophage function, both at baseline and in response to resistance exercise, that may limit muscle hypertrophy in older adults...

Research Grants30

  1. Alerations of Sleep and Circadian Timing in Aging
    Eve Van Cauter; Fiscal Year: 2013
    ..Core B (Methods and Analysis) will standard operating procedures for data collection, archival and analysis. Core C will assay peripheral levels of hormones, cytokines and other blood constituents. ..