TTUHSC Garrison Institute
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Research Projects

The following are some of the GIA's current and recent aging projects and publications.

Research Projects

July 2007 to April 2012 - NIH: "Vascular-mediated neuronal death in Alzheimer's." Amount : $1.25 million

August 2006 to July 2010 - NIH: "Vascular Inflammation in the Aging Brain." Amount: $1,339,464

2006 and ongoing - D.W. Reynolds Foundation: "Comprehensive Competency-based Program to Strengthen Physicians Training." Amount: $1,999,502

September 2004 to December 2008 NIH: "Is There a Link Between Alzheimer's and Atherosclerosis." Amount: $783,576

December 2005 to September 2007 - McNeil Pharmaceuticals: "Vascular-mediated Neurodegeneration: A Novel Target for Acetaminophen." Amount: $75,000

2006 - McNeil Consumer and Spec Pharmaceuticals: "Vascular-Mediated Neurodegeneration/Alzheimer's: A novel Target for Acetaminophen." Amount $75,000

November 2006 to October 2007 - King Foundation, Cochran County Aging Study, Amount: $58,402

2005 - Texas Department of Aging and Disability Services: "Long Term Care Facility Technology Readiness Program XCFDA." Amount $72,986

2005 - Texas Department of Aging and Disability Services: "Geriatric Education Training Academy." Amount: $48,745.

2005 - Texas Department of Aging and Disability Services/PHS/HRSA: "Long Term Care Demonstration Project 93.778:" Amount: $75,000

2005 - Texas Coordinating Board/Texas Consortium of Alzheimer's/UTMBH: "Texas Consortium of Alzheimer's Disease Centers XCFDA." Amount: $25,000

2005 - NIH/National Institute on Aging: "Cox2-Regulated Testosterone Biosynthesis in Male Aging." Amount: $1,113,750

Publications

Wang S, Miller B, Matthan NR, Wu D, Reed D, Yin X, Grammas P, Moustaid-Moussa N, Shen C, Lictenstein AH. Enhanced lipid accumulation in hepatic and gonadal adipose tissue resulting from an atherogenic diet is positively associated with systemic inflammation and aortic cholesterol accumulation in LDL receptor null mice. Nutri Metab, [Submitted], 2013.

Luo J, Yin X, Sanchez A, Tripathy D, Martinez J, Grammas P. Chapter 32:  Purification of Endothelial Cells from the Rat Brain. Met Mol Biol, [In Press], 2013.

Sanchez A, Tripathy D, Yin X, Luo J, Martinez J, Grammas P. Sunitinib enhances neuronal survival in vitro via NF-κB-mediated signaling and expression of cyclooxygenase-2 and inducible nitric oxide synthase. J Neuroinflammation, 10:93, 2013.

Tripathy D, Sanchez A, Yin X, Luo J, Martinez J, Grammas P. Thrombin, a mediator of cerebrovascular inflammation in AD and hypoxia. Front Aging Neurosci, 5:19, 2013.

Wang S, Matthan NR, Wu D, Reed DB, Bapat P, Yin X, Grammas P, Shen CL, Lichtenstein AH. Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios. Clin Nutr, [epub ahead of print] April 2013.

Sanchez A, Tripathy D, Luo J, Yin X, Martinez J, Grammas P. Neurovascular unit and the effects of dosage in VEGF toxicity: role for oxidative stress and thrombin. J Alz Dis, 34:281-291, 2013.

O’bryant SE, Xiao G, Barber R, Cullum CM, Weiner M, Hall J, Edwards M, Grammas P, Wilhelmsen K, Doody R, Diaz-Arrastia R, Texas Alzheimer’s Research Consortium. Molecular neuropsychology: Creation of test-specific blood biomarker algorithms. Dement Geriatr Cogn, [DOI:10.1159/000345605], 2012.

Tripathy D, Sanchez A, Xiangling L, Martinez J, Grammas P. Age-related decrease in cerebrovascular-derived neuroprotective proteins: effect of acetaminophen. Microvas. Res, 84:278-285, 2012.

Sanchez A, Tripathy D, Yin X, Desobry K, Martinez J, Riley J, Gay D, Luo J, Grammas P. p38 MAPK, a mediator of hypoxia-induced cerebrovascular inflammation. J Alz Dis, 32:587-597, 2012.

Wang S, Qaisar U, Yin X, Grammas P. Gene expression profiling in Alzheimer’s disease brain microvessels, J Alz Dis, 31:193-205, 2012.

Luo J, Martinez J, Yin X, Sanchez A, Tripathy D, Grammas P. Hypoxia induces angiogenic factors in brain microvascular endothelial cells. Microvas Res, 83:138-145, 2012.

O’Bryant SE, Xiao G, Barber R, Huebinger, R, Wilhelmsen K, Edwards M, Graff-Radford N, Doody R, Diaz-Arrastia R, Texas Alzheimer’s Research Consortium. A blood-based algorithm for the detection of Alzheimer’s disease. Dement Geriatr Cogn Disord, 32:55-62, 2011.

O’Bryant SE, Xiao G, Barber R, Reisch J, Hall J, Cullum CM, Doody R, Fairchild T, Adams P, Wilhelmsen K, Diaz-Arrastia R, Texas Alzheimer’s Research Consortium. A blood-based screening tool for Alzheimer’s disease that spans serum and plasma. Alzheimer’s Disease Neuroimaging Initiative,6:e28092, 2011

Sanchez A, Tripathy D, Yin X,  Luo J, Martinez J, Grammas P.  Pigment epithelium-derived factor (PEDF) protects cortical neurons in vitro from oxidant injury by activation of extracellular signal-regulated kinase (ERK) 1/2 and induction of Bcl-2. Neurosci Res, 1:1-8, 2011.

Grammas P. The vasculature in Alzheimer’s disease: a new therapeutic target for an old disease? Therapy, 8:463-465, 2011.

Grammas P, Tripathy D, Sanchez A, Yin X, Luo J. Brain microvasculature and hypoxia-related proteins in Alzheimer’s disease. Int J Clin Exp Pathol, 4:616-27, 2011.

Grammas P, Martinez J, Miller B. Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases. Expert Rev Mol Med 13:E19, 2011.

Grammas, P. Neurovascular dysfunction, inflammation and endothelial activation: Implications for the pathogenesis of Alzheimer’s disease. J Neuroinflammation, 8:26, 2011.

Grammas P. Angiogenic mediators and the pathogenesis of Alzheimer’s disease. In Therapeutic Angiogenesis for Vascular Diseases. Slevin, M, ed, Springer, 1st Edition, 2011, XVI.

Li W, Pandey A, Yin X, Chen J, Stocco D, Grammas, P.  Effects of Apigenin on steriodogenesis and steroidogenic acute regulatory gene expression in leydig cells. J Nutr Biochem, 3:212-8, 2011.

Grammas P, Sanchez A, Tripathy D, Luo J, Martinez J. Vascular signaling abnormalities in Alzheimer’s disease. Cleve Clin J Med, 78:S50-S53, 2011.

O’Bryant SE, Hobson VL, Hall JR, Barber RC, Zhang S, Johnson L, Diaz-Arrastia R, Texas Alzheimer’s Research Consortium. Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer’s disease cases. Dement Geriatr Cogn Disord, 1:31-6, 2011.

O’Bryant SE, Xiao G, Barber R, Reisch J, Doody R, Fairchild T, Adams P, Waring S, Diaz-Arrastia R, Texas Alzheimer’s Research Consortium. A serum protein-based algorithm for the detection of Alzheimer’s disease. Arch Neurol, 9:1077-81, 2010.

Tripathy D, Yin X, Sanchez A, Luo J, Martinez J, Grammas P. Cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging. J Neuroinflammation, 7:63, 2010

Evola M, Hall A, Wall T, Young A, Grammas, P. Oxidative stress impairs learning and memory in apoE knockout mice.  Pharmacol Biochem Behav, 96:181-6, 2010.

Luo J, Grammas P. Endothelin-1 is elevated in Alzheimer’s disease brain microvessels and in neuroprotective. J Alz Dis, 21:887-96, 2010.

Sanchez  A,  Wadhani S, Grammas, P.  Multiple neurotrophic effects of VEGF on cultured neurons. Neuroscience Research, 44:323-331,2010.

Tomashevski A, Webster DR, Grammas P, Kruman II. Cyclin –C-dependent cell-cycle entry is required for activation of non-homologous end joining DNA repair in postmitotic neurons. Cell Death Differ, 17:1189-98, 2010.

Yin X, Wright J, Wall T, Grammas P. Brain endothelial cells synthesis neurotoxic thrombin in Alzheimer’s disease. Am J Path, 176:1600-6, 2010.

Tripathy D, Thirumangalakudi l, and Grammas, P.  RANTES upregulation in the Alzheimer’s disease brain: a possible neuroprotective role. Neurobiol Aging 31: 8-16, 2010

Pandey A, Yin X, Stocco D, Grammas P, Wang X.  Blocking L-type calcium channels reduced the threshold of cyclic AMP-induced steroidogenic acute regulatory gene expression in MA-10 mouse Leydig cells. J Endocrinol, 204:67-74, 2010

Sanchez A, Tripathy D, Grammas P.  RANTES release contributes to the protective action of PACAP38 against sodium nitroprusside in cortical neurons. Neuropeptides, 43:315-320, 2009.

Pandey AK, Yin X, Schiffer RB, Hutson, JC, Stocco,DM, Grammas P, Wang, X. Involvement of the Thromboxane A2 receptor in the regulation of steroidogenic acute regulatory gene expression in Murine Leydig cells. Endocrinology, 7:3267-73, 2009.

Tripathy D, Grammas P. Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress. Journal of Neuroinflammation, 6:10, 2009.

Tripathy D, Grammas P. Acetaminophen protects brain endothelial cells against oxidative stress.   Microvascular Research, 77:289-296, 2009.

Thirumangalakudi L, Vittal Rao H, Grammas P. Involvement of PGE2 and PGDH but not COX-2 in thrombin-induced cortical neuron apoptosis. Neuroscience Letters, 452:172-175, 2009.

Vittal Rao H, Thirumangalakudi L, Grammas P. Cyclin C and cyclin dependent kinanses 1,2, and 3 in thrombin-induced neuronal cell cycle progession and apoptosis.  Neuroscience Letters, 450:347-350, 2009.

Sanchez A, Vittal Rao, H, Grammas P.  PACAP38 protect rat cortical neurons against the neurotoxicity evoked by sodium nitroprusside and thrombin. Regulatory Peptides, 152:33- 40, 2009.

Sanchez A, Chrivia-Internati M, Grammas P. Transduction of PACAP38 protexts primary cortical neurons from neurotoxic injury. Neurosci Letters, 448:52-5, 2008.

O’Bryant SE, Grammas P.  A case for the creation of a biomarker-based algorithm for the detection of Alzheimer’s disease. Texas Public Health Journal, Special Issue on the Texas Alzheimer’s Research Consortium, 60:15-18, 2008.

Christov A, Ottman T, Hamdheydari L, Grammas P.  Structural changes in Alzheimer’s disease brain microvessels. Current Alz Res 5:392-395, 2008.

Jana K, Yin X, Schiffer R, Chen J, Pandey A, Stocco D, Wang X and Grammas P. Chrysin, a natural flavonoid enhances steroidogenesis andsteroidogenic acute regulatory protein gene expression in mouse Leydig cells. J Endocrinology 197:315-32, 2008.

Grammas P, Nutt J, Johanson C, Stopa E, Quinn J, Maron L, Sah D, Wu J, Leenders N, Zlokovic B. Neurodegeneration and the Brain Barriers. http://www.ibbsoc.org/PDFs/Neurodegneration.pdf.

Neuwelt E, Abbott NJ, Abrey L, Banks WA, Blakley B, Davis T, Engelhardt B, Grammas P, Nedergaard M, Nutt J, Pardridge W, Rosenberg GA, Smith Q, Drewes LR.  Strategies to advance translational research into brain barriers. Lancet Neurol, 7:84-96, 2008.

Wang X, Tin X, Schiffer RB, King SR, Stocco DM, Grammas P. Inhibition of Thromboxane A synthase activity enhances steroidogenesis and steroidogenic acute regulatory gene expression in MA-10 mouse leydig cells. Endocrinology, 149:851-857, 2008.

Vittal-Rao H, Thirumangakudi L, Desmond P, Grammas P. Cyckin D1, Cdk4 and Bim mediate thrombin-induced apoptosis in cultured cortical neurons. J Neurochem, 10: 498-505, 2007.

Thirumangakudi L, Yin L, Vittal-Rao H, Grammas P. IL-8 induces expression of matrix metalloproteinases, cell cycle and pro-apoptotic proteins, and cell death in cultured neurons. >J Alz Dis,>11:305-311, 2007.

Triapthy D, Thirumangalakudi L, Grammas P. Expression of macrophage inflammatory protein 1-is elevated in Alzheimer’s vessels and is regulated by oxidative stress.:J Alz Dis, : 447-55.

Christov A, Ottman T, Hamdheydari L, Grammas P.  Structural changes in Alzheimer’s disease brain microvessels. Submitted

Sanchez A, Chiriva-Internati M, Grammas P. Adeno-associated viral gene transfer of PCAP38 to primary cortical neurons increases neuronal survival in vitro. Submitted

Tripathy D, Sanchez A, Thirumangalakudi L, Grammas P. RANTES upregulation in the Alzheimer’s disease brain: a possible neuroprotective role. Submitted

Kruman, II  and Schwartz, EI (2008). DNA damage response and neuroprotection. Frontiers in Bioscience [Invited review]. 13:2504-2515.

Schwartz, EI,  Smilenov, LB,  Price, MA,  Osredkar, T, Baker, RA,  Ghosh, S,  Vollmer, TI., Shi, F-D, Lencinas, A., Stearns, DM., Gorospe, M, and Kruman, II (2007). Cell Cycle Activation in Postmitotic Neurons is essential for DNA Repair. Cell Cycle. 6(3): 318-329.

Kruman II., Mouton, PR, Emokpae, R.,Jr. , Roy G. Cutler RC., and Mattson, MP. (2005). Folate Deficiency Inhibits Proliferation of Adult Hippocampal Progenitors. NeuroReport 16:1055-1059.

Endres M, Ahmadi M, Kruman I, Biniszkiewicz D, Meisel A, Gertz K.(2005). Folate deficiency increases postischemic brain injury. Stroke. 36(2):321-325.

Kruman, I.I. Why Do Neurons Enter the Cell Cycle? (2004). Cell Cycle [Invited review]. 3:769-773.

Kruman, I.I., Wersto, R.P., Cardozo-Pelaez,F., Smilenov, L., Chan, S.L., Chrest, F.J.,  Emokpae, R.,Jr.,  Gorospe,M., and Mark P Mattson (2004). Cell cycle activation linked for neuronal cell death induced by DNA damage. Neuron 41:549-561.

Kruman, I.I.,  Schwartz, E.,  Kruman, Y. ,  Cutler, R.,   Zhu, X., Nigel H. Greig, N.H. , and   Mattson, M.P. (2004) Suppression of Uracil-DNA Glycosylase Induces Neuronal Apoptosis. J.Biol.Chem. 279:43952-43960.

Kruman, I.I., Kumaravel, T., Lohani , A. Haughey, N., Pedersen, W.,  Evans, M., and   Mattson, M.P.(2002). Homocysteine and folic acid deficiency enhance  A toxicity by DNA repair impairment. Implication in pathogenesis of neurodegeneration  J. Neuroscience  22:1752-1762.

Mattson, M.P., Kruman I.I, and Duan,W. (2002). Folic acid and homocysteine in age-related disease. Ageing Res. Rev. 1:95-112.

Duan, W., Ladenheim, B., Cutler, R.G., Kruman, I.I., Cadet, J.L., Mattson, M.P. (2002).  Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. J Neurochem. 2002.  80:101-10

Turchan, J., Anderson, C., Hauser, K.F., Sun, Q., Zhang, J., Liu, Y., Wise, P.M., Kruman, I., Maragos, W., Mattson, M.P., Booze, R., Nath a. (2001). Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine. BMC Neurosci.  2:3-

Kruman, I.I., Culmsee, C., Chan,S., Kruman,Y., Guo, Z., Penix,L., and Mattson, M.P. (2000). Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J. Neurosci. 20:6920-6926.

Pedersen, W.A., Luo, H., Kruman, I.I., Kasarskis, E.,and Mattson, M.P. (2000) Evidence that the prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis". FASEB J. 14:913-924.

Guo,Z., Kindy, M.S.,  Kruman, I.I. and Mattson, M.P.  (2000) ALS-linked Cu/Zn-SOD mutation impairs cerebral synaptic glucose and glutamate uptake and exacebrates ischemic injury. J. Cereb. Blood Flow Metab 20:463-468.

Kruman, I.I., Pedersen, W., Springer, J.E., and Mattson, M.P. (1999) ALS-linked Cu/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism  involving increased oxidative stress and perturbed calcium homeostasis. Exp. Neurol. 160:28-39.

Kruman, I.I., Nath, A., Maragos, W.F., Chan, S.L., Jones, M., Rangnekar,V.M.,  Jakel, R. J., and Mattson, M.P. (1999) Evidence that Par-4 participates in pathogenesis of HIV-encephalitis . Am. J. Pathol. 155:39-46.

Kruman I.I., Nath A., Mattson M.P. (1998) HIV protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload and oxidative stress. Exp. Neurol. 154:276-288.

Kruman I.I. and  Mattson, M.P. (1999) Pivotal role of mitochondrial calcium uptake in neural cell apoptosis and necrosis. J. Neurochem.  72:529-540. 

Kruman I.I., Guo Q., Mattson M.P. (1998) Calcium and peroxynitrite mediate staurosporine-induced mitochondrial dysfunction and apoptosis in neural cells. J.Neurosci.Res. 51: 293-308.

Gordon R.Ya., Bocharova L.S., Kruman I.I., Popov V.I., Kazantsev A.P., Khutzian S.S., Karnaukhov,V.N. (1997) Acridin orange as an indicator of ribosome state in a cell. Cytometry. 29:215-221.

Mark, R.J., Keller, J.N., Kruman, I.I., Mattson, M.P. (1997) Basic FGF attenuates amyloid b-peptide-induced oxidative stress, mitochondrial dysfunction, and impairment of Na+/k+-ATPase activity in hippocampal neurons. Brain Res.736:205-214.

Kruman, I.I., Bruce-Keller, A.J., Bredesen, D, Waeg, G., Mattson, M.P. (1997) Evidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal apoptosis. J. Neurosci. 17:5089-5100.

Abstracts

Tripathy D, Thirumangalakudi L, Grammas P. MIP-1? expression is elevated in Alzheimer’s vessels and is regulated by oxidative and lipid stress. FASEB 2007.

Desmond P, Evola M,  Young A, Grammas P. Oxidative stress impairs learning and memory in ApoE knockout mice. FASEB 2007.

Sanchez A, Grammas P. PACAP38 protects against sodium nitroprusside-induced apoptosis in rat cortical neurons. FASEB 2007.

Desmond P, Evola M,  Young A, Grammas P. Oxidative stress impairs learning and memory in ApoE knockout mice. TTUHSC Researchers Symposium 2007.

Wall T, Brown G, Grammas P.Oxidative stress and Alzheimer’s disease increase inflammatory protein expression in brain microvessels. TTUHSC Researchers Symposium 2007.

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