Updated Publication List

PROJECT 1

Original Papers:

1. Koulen P, Madry C, Duncan RS, Hwang JY, Nixon E, McClung N, Singh M. 2008 Progesterone potentiates IP3-mediated calcium signaling through Akt/PKB signaling. Cellular Physiology and Biochemistry 21:161-72. 2. Hwang J-Y, Duncan RS, Madry C, Singh M, Koulen P. 2009 Progesterone Potentiates Calcium Release Through IP3 Receptor by an Akt-Mediated Mechanism in Hippocampal Neurons. Cell Calcium 45:233-42 3. Jodhka PK, Kaur P, Underwood W, Lydon JP, Singh M. 2009. The differences in neuroprotective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression. Endocrinology. 150(7):3162-8. (PMCID #: 2703540) 4. Huang R, Singh M, Dillon GH. 2010 Genistein directly inhibits native and recombinant NMDA receptors. Neuropharmacology. Mar 18. PMCID # PCM2861344 5. Su C, Underwood WA, Rybalchenko N, and Singh M. 2011 ERK1/2 and ERK5 have distinct regulatory roles in BDNF transcriptional regulation. J. Neuroscience Research 89(10):1542- 50. 6. Hilburn C, Nejtek VA, Davis W, Singh M, Patel G, Gangswani P, Forster MJ. 2011 Is Serum brain-derived neurotrophic factor related to self-reported craving or substance use in alcohol, cocaine, or methamphetamine-dependent subjects? Neuropsychiatr Dis Treat (in press) 7. Cunningham RL, Macheda T, Watts LT, Poteet E, Singh M, Roberts JL, Giuffrida A. 2011 Androgens exacerbate motor asymmetry in male rats with unilateral 6-hydroxydopamine lesion. Hormones and Behavior (E-pub ahead of print) – PMID 21907204 8. Mirshams N, Rybalchenko N, Singh M. The cytoprotective effects of DHT are mediated by the estrogen receptor-activating metabolite, 3beta diol. (Pending review). 9. Su C, Rybalchenko N, Cunningham R and Singh M. Progesterone increases the release of Brain-derived Neurotrophin Factor from Glia via Progesterone Receptor Membrane Component 1 (Pgrmc1)-dependent ERK5 signaling (submitted to Pfizer for review – based on conditions of a Material Transfer Agreement)

Reviews

10. Singh M. 2007. Progestins and Neuroprotection: Are all progestins created equal? Minerva Endocrinologica 32(2):95-102 11. Singh M, Sumien N, Kyser C and Simpkins JW. 2008. Estrogens and Progestins as neuroprotectants: What animal models teach us. Frontiers in Bioscience 13:1083-89. 12. Simpkins JW and Singh M. 2008. “More than a Decade of Estrogen Neuroprotection”, in Challenges in the development of novel steroids as treatments for Alzheimer’s disease: A perspective. Alzheimer’s & Dementia 4:S131-36. 13. Dohi A, Dillon GH and Singh M. 2008. Neurosteroids and premenstrual disorders of affect, in Neuroactive Steroids in Brain Functions, and Mental Health: New Perspectives for Research and Treatment. Michael Ritsner and Abraham Weizman (Eds) Springer. pp 483- 491 14. Singh M 2009. Neuroprotection: Pharmacological Approaches. Encyclopedia of Neuroscience, (Larry Squire Editor). Oxford: Academic Press

1 15. Simpkins JW, Perez E, Wang X, Yang S-H, Wen Y and Singh M. 2009 The potential for estrogens in preventing Alzheimer’s disease and vascular dementia. Therapeutic Advances in Neurological Disorders 2(1):31-49. 16. Singh M 2011. Progestins and Neuroprotection: Why the choice of progestin matters in “Hormones in Neurodegeneration, Neuroprotection and Neurogenesis”, Mellon, S. H. and Gravanis, A. (Eds). Wiley-Blackwell Publishing. pp 29-40.

Abstracts Submitted or Published in 2011:

1. Su C, Rybalchenko N and Singh M. 2011. Erk1/2 and erk5 have distinct regulatory roles in bdnf transcriptional regulation. Society for Neuroscience Abstract 2. Singh M and Su C. The role of Pgrmc1 and ERK5 in mediating progesterone-induced BDNF release. 2011. Society for Neuroscience Abstract. 3. Cunningham RL, Macheda T, Poteet E, Lechleiter JD, Giuffrida A and Singh M. 2011. Androgens alter dopamine neuronal-dependent behaviors in male rats with unilateral 6- hydroxydopamine lesions. Society for Neuroscience abstract 4. Badeaux A. and Singh M. 2011. The membrane androgen receptor as a therapeutic target for glioblastoma. Society for Neuroscience Abstract.

PROJECT 2

Original Papers

1. Xia M., Shaohua Yang, James W. Simpkins, Hanli Liu, Noninvasive Monitoring of Estrogen Effects against Ischemic Stroke in Rats by Near Infrared Spectroscopy, Applied Optics 46: 8315-8321, 2007. PMID 18059674 2. Mao, X., S.H. Yang, J. W. Simpkins and S W. Barger, Glutamate receptor activation evokes calpain-mediated degradation of Sp3 and Sp4, the prominent Sp-family transcription factors in neurons, J Neurochemistry 100: 1300-1314, 2007. PMID 17316402; PMC1949346 3. Yi Wen, Shaohua Yang, Ran Liu, Evelyn Perez, Anne Marie Brun-Zinkernagel, Peter Koulen and James W. Simpkins Cdk5 is involved in NFT-like tauopathy Induced by Transient Cerebral Ischemia in Female Rats, Biochem Biophysica Acta 1772: 473-383, 2007. PMID 17113760 4. Liu, R., S. H. Yang , J. Cutright, K.D. Yi , X Wang , Y-J Hu, A. L. Day, J. W. Simpkins, Dose dependence and therapeutic window for the neuroprotective effects of 17 b- estradiol when administered after cerebral ischemia, Neuroscience Letters 415: 237- 241, 2007. PMID 17331646; PMC1936945 5. Jung, M.E., R Agarwal, and J.W. Simpkins, Ethanol withdrawal posttranslationally decreases the activity of cytochrome c oxidase in an estrogen reversible manner, Neuroscience Letters 416: 160-164, 2007. PMID 17320290; PMC2081971 6. Tesco G, Young Ho Koh, Eugene Kang, Andrew Cameron, Shinjita Das, Miguel Sena- Esteves, Mikko Hiltunen, Shao-Hua Yang, Zhenyu Zhong, Yong Shen, James Simpkins and Rudolph E. Tanzi, Depletion of GGA3 stabilizes BACE and enhances b-secretase activity. Neuron. 54:721-737, 2007. PMID 17512984

2 7. John A. Schetz, Evelyn Perez, Shiuhwei Chen, Ran Liu and James Simpkins, A prototypical sigma-1 receptor antagonist protects against brain ischemia, Brain Research 1181: 1-9, 2007. PMID 17919467 8. Arti B. Sharma, Matthew A. Barlow, Shao-Hua Yang, James W. Simpkins, Robert T. Mallet, Pyruvate Enhances Neurological Recovery Following Cardiopulmonary Arrest and Resuscitation, Resuscitation 76:108-119, 2008. PMID 17618729; PMC2737333 9. Prokai-Tatrai K, Perjesi P, Rivera-Portalatin NM, Simpkins JW, Prokai L., Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. Steroids 73: 280-288, 2008. PMID 18068745; PMC2317824 10. Yi K D, Zu Yun Cai, Douglas F. Covey, and James W. Simpkins, Receptor-Independent Mechanism for Estrogen Neuroprotection via protein phosphatase preservation and attenuation of persistent ERK1/2 activation, J Pharmacol Exp Ther. 324:1188-1195. 2008. PMID 18089844 11. Jung, M.E., Yan, L-J., Forster, M.J. and Simpkins, J.W. Ethanol withdrawal provokes mitochondrial injury in an estrogen preventable manner. J Bioenerg Biomembr. 40: 35- 44. 2008. PMID 18210193 12. Jung ME, Simpkins JW, Wilson AM, Downey HF, Mallet RT. Intermittent Hypoxia Conditioning Prevents Behavioral Deficit and Brain Oxidative Stress in Ethanol Withdrawn Rats. J Appl Physiol. 105:510-517, 2008. PMID: 18499779; PMC2519950 13. D. Maneesh Kumar, James W. Simpkins and Neeraj Agarwal, Estrogens as Retinal Neuroprotectants, Molecular Vision 14: 1480-1486, 2008. PMID 18698377; PMC2507727 14. Sarkar, S., R.-Q. Huang, S. Logan, G.H. Dillon and J.W. Simpkins, Estrogens directly potentiate neuronal L-type Ca2 channels, Proceedings of the National Academy of Sciences, USA 105: 15148-15153, 2008. PMID 18815371; PMC2575342 15. Yi KD, Covey DF, Simpkins JW. Mechanism of Okadaic Acid Induced Neuronal Death and the Effect of Estrogens. J Neurochem. 108: 732-740, 2008. PMID: 19054278; PMC2727740 16. Jung ME, Wilson AM, Ju X, Wen Y, Metzger DB, Simpkins JW. Ethanol withdrawal provokes opening of the mitochondrial membrane permeability transition pore in an estrogen preventable manner. J Pharmacol Exp Ther. 328: 692-698, 2008. PMID 19050172; PMC2682266 17. Kun Don Yi and James W. Simpkins, PP1, PP2A, and Calcineurin Play a Role in Estrogen-mediated Neuroprotection, Endocrinology 149: 5235-5243, 2008. PMID 18566123; PMC2582922 18. Shao-Hua Yang, Saumyendra N. Sarkar, Ran Liu, Evelyn Perez, Xiaofei Wang, James W. Simpkins Estrogen receptor beta is a mitochondrial vulnerability factor, J Biol Chem 284: 9540-9548, 2009. PMID 19189968; PMC2666606 19. Prokai-Tatrai, K., L. Proka, James W. Simpkins and Marianna E. Jung, Phenolic compounds protect cultured hippocampal neurons against ethanol-induced oxidative stress, Int. J. Mol. Sci. 10: 1773-1787, 2009. PMID 19468338; PMC2680646 20. Marianna E. Jung, Xiaohua Ju, James W. Simpkins, Daniel B. Metzger, Liang-Jun Yan, Yi Wen, Ethanol withdrawal acts as an age-specific stressor to activate cerebellar P38 kinase, Neurobiology of Aging, 2010 Jan 30. [Epub ahead of print]. 21. Liu R, Liu Q, He S, Simpkins JW, Yang S., Combination therapy of 17{beta}-estradiol and recombinant tissue plasminogen activator for experimental ischemic stroke. J Pharmacol Exp Ther. 332: 1006-1012, 2010. PMID 19952306; PMC2835431 22. Gatson, J. W., D. L. Maass, J. W. Simpkins, A. H. Idris, J. P. Minei, J. G. Wigginton, Estrogen Treatment Following Severe Burn Injury Reduces Brain Inflammation and

3 Apoptotic Signaling, Submitted to the Journal of Neuroinflammation, 6: 1-10, 2009. PMID 19849845; PMC2774304 23. Hien P. Nguyen, Samuel H. Yang, Jane G. Wigginton, James W. Simpkins, Kevin A. Schug, Retention behavior of estrogen compounds on hydrophilic interaction chromatography stationary phases coupled with electrospray ionization mass spectrometry (HILIC-ESI-MS), Journal of Separation Science 33, 793–802, 2010. PMID 20201045 24. Zhang Z. and J. W. Simpkins, Okadaic acid induces tau phosphorylation in SH-SY-5Y cells in an estrogen-preventable manner, Brain Res. 23: 1345:176-181, 2010. PMID 20457142; PMC2913890 25. Zhang Zhang and James W. Simpkins, An okadaic acid induced model of tauopathy and cognitive deficiency, Brain Res. 1359: 233-246, 2010. PMID 20807517 26. Sarkar, S. L. N Smith, S. Logan, and J. W. Simpkins, Estrogen-Induced Activation of Extracellular Signal-Regulated Kinase (ERK) Signaling Triggers Dendritic Resident mRNA Translation, Neuroscience 170: 1080-1085, 2010. PMID 20691769; PMC3026564 27. Nguyen, H. P., Li Li, Joshua W. Gatson, David Maass, Jane G. Wigginton, James W. Simpkins, Kevin A. Schug, Simultaneous quantification of four native estrogen hormones at trace levels in human cerebrospinal fluid using liquid chromatography- tandem mass spectrometry, J. Pharm Biomed. Anal. 54: 830-837, 2011. PMID 21145681 28. Gatson, J. W., J. W. Simpkins, K.D. Yi, A. H. Idris, J. P. Minei, J. G. Wigginton, Aromatase is Increased in Astrocytes in the Presence of Elevated Pressure, Endocrinology 152: 207-213, 2011. PMID 21111714; PMC3048764 29. Logan SM, Sarkar SN, Zhang Z, Simpkins JW, Estrogen-induced Signaling Attenuates Soluble Aβ Peptide-Mediated Dysfunction of Pathways in Synaptic Plasticity. Brain Res. Brain Research 1383: 1 – 12, 2011. PMID 21262203; PMC3065978 30. Marianna E. Jung, Xiaohua Ju, Daniel B. Metzger, James W. Simpkins, Ethanol withdrawal hastens the aging of cytochrome c oxidase, Neurobiology of Aging, Mar 23. [Epub ahead of print]. 31. Hien P. Nguyen, Lauren Tedmon, Li Li, Jane G. Wigginton, David Maass, Joshua W. Gatson, James W. Simpkins, Kevin A. Schug, Investigation of the Temperature Stability of Premarin Intravenous using Liquid Chromatography – Mass Spectrometry, Journal of Pharmaceutical and Biomedical Analysis Journal of Pharmaceutical and Biomedical Analysis 55: 1218-1222, 2011. 32. Wen Y, Li W, Poteet E, Xie L, Tan C, Yan, L, Glodberg M, Marvin M, Simpkins JW, Yang SH. Alternative Mitochondrial Electron Transfer as a Novel Strategy for Neuroprotection. J. Biol. Chem. 2011 286: 16504-16515. 33. Richardson, T.E., S.-H. Yang, Y. Wen and J. W. Simpkins, Estrogen protection in Friedreich’s ataxia skin fibroblasts, Endocrinology 152: 2742-2749, 2011. Epub 2011 May 3. PMID: 21540287 34. Xie L, Poteet E, Hadley A, Liu R, Wen Y, Simpkins JW, Yang SH. Modulation of polymorphonuclear neutrophil functions by astrocyte. 2010, Journal of Neuroinflammation, 2010 Sep 9;7(1):53. [Epub ahead of print]PMID: 20828397. 35. Jung ME, Ju X, Simpkins JW, Metzger DB, Yan LJ, Wen Y., Ethanol withdrawal acts as an age-specific stressor to activate cerebellar P38 kinase. Neurobiol Aging. 32:2266- 2278. 2011.

4 Reviews

36. Perez, E., X. Wang and J.W. Simpkins, Role of Antioxidant activity of estrogens in their potent neuroprotection, submitted Oxidative Stress and Neurological Disorders, Editor, G. Ali Queshi, Elsevier Publishing Company, Holland, pp 497-518, 2007.

37. Prokai, L., and J. W. Simpkins, Structure-non-genomic neuroprotection relationship of estrogens and estrogen-derived compounds, Pharmacology & Therapeutics 114: 1-12, 2007. PMID 17336390; PMC1905848 38. Simpkins, J.W. and J. A. Dykens, Mitochondrial mechanisms of estrogen neuroprotection. Brain Research Reviews 57: 421-430, 2008. PMID 17512984 39. Singh, M., C. Kyser, N. Sumien, J. W. Simpkins, Estrogens and Progesterone as Neuroprotectants: What animal models teach us, Frontiers in Neurobiology, 13:1083- 1089. 2008. PMID 17981614; PMC2586167 40. James W. Simpkins and Meharvan Singh, More Than a Decade of Estrogen Neuroprotection, Alzheimer’s & Dementia 4: S131-S136, 2008. PMID 18631989 41. Simpkins, J. W., Protecting the brain from aging and insult. Journal of Medical Sciences 1: 29-32, 2008. 42. James W. Simpkins, ShaoHua Yang, Saumyendra N. Sarkar and Virginia Pearce, 43. Estrogen Actions on Mitochondria-Physiological and Pathological Implications, Molecular and Cellular Endocrinology 290(1-2):51-59, 2008. PMID 18571833; PMC2737506 44. James W. Simpkins, Evelyn Perez, X. Wang, ShaoHua Yang, Yi Wen and Meharvan Singh, The Potential for Estrogens in Preventing Alzheimer’s Disease, Therapeutic Advances in Neurological Disorders 2: 31-49, 2009. PMID 19890493; PMC2771945 45. James W. Simpkins, Joshua W. Gatson, and Jane G. Wigginton, Rationale and Recommendations for First Evaluating Anti-Alzheimer’s Medications in Acute Brain Injury Patients, Alzheimer’s and Dementia 5: 143-146, 2009. PMID 19328446 46. James W. Simpkins, Evelyn Perez, X. Wang, ShaoHua Yang, Yi Wen and Meharvan Singh, The Potential for Estrogens in Preventing Alzheimer’s Disease, Therapeutic Advances in Neurological Disorders 2: 31-49, 2009. PMID 19890493; PMC2771945 47. James W. Simpkins, Kon Don Yi, and ShaoHua Yang, Role of Protein Phosphatases and Mitochondria in the Neuroprotective Effects of Estrogens, Frontiers in Neuroendocrinology, 30: 93-105, 2009. PMID 19410596; PMC2835549 48. Simpkins JW, Yi KD, Yang SH, Dykens JA., Mitochondrial mechanisms of estrogen neuroprotection. Biochim Biophys Acta. 1800: 1113-1120, 2010. PMID 19931595; PMC2889195 49. James W. Simpkins, Brian J. Balin, and Brian E. Wood, Alzheimer’s Disease: The Crisis in Upon Us, J. American Osteopathic Association 110: S1-S3, 2010. PMID 20926744 50. ILL-Raga G, Eva Ramos-Fernández, Francesc X. Guix, Marta Tajes, Mònica Bosch, Ernest Palomer, Juan Godoy, Sebastián Belmar, Waldo Cerpa, James W. Simpkins, Nibaldo C. Inestrosa, and Francisco J. Muñoz, Amyloid ß-peptide fibrils induce nitro- oxidative stress in neuronal cells, J Alzheimers Dis. 22: 641-652, 2010. PMID 20858976 51. Yi, K.D., E. Perez, S.-H. Yang, R. Liu, D.L. Covey and J.W. Simpkins, The assessment of non-feminizing estrogens for use in neuroportection, Brain Research Reviews 1379: 61-70, 2011. PMID: 21111714; PMC3048764 52. Walf AA, Paris JJ, Rhodes ME, Simpkins JW, Frye CA. Divergent mechanisms for trophic actions of estrogens in the brain and peripheral tissues. Brain Res 1379:119-36, 2011. PMID 21111714; PMC3048764

5 53. Simpkins JW, Yi KD, Perez E, Covey DF. Structure-Nongenomic Neuroprotection Relationship of Estrogens and Estrogen-Derived Compounds. Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis. Eds AG Gravanis and SH Mellon, Wiley Publishers, Pages 13-28, 2011. 54. Shao-Hua Yang and James W. Simpkins, Ischemia-Reperfusion Promotes Tau and Beta-Amyloid Pathology and a Progressive Cognitive Impairment, in Ischemia- Reperfusion Pathways in Alzheimer’s Disease, Ed. Ryszard Pluta, Nova Science Publications, In Press, 2011.

Opinions

55. Simpkins, J.W., Brain Rusting: The Paradox of Life on the Edge" the Kronos Longevity Kronical, 8: 8-10, 2007. 56. Paul Aisen, Marilyn Albert, John C.S. Breitner, Neil Buckholtz, Jodey P. Corey-Bloom, Jeffrey L. Cummings, Rachelle Doody, Bill Evans, Steven Ferris, Howard Fillit, Norman Foster, Richard A. Frank, Doug Galasko, Serge Gauthier, Sid Gilman, Barry Greenberg, Michael Grundman, Bradley Hyman, Claudia Kawas, Jeffrey Kaye, Ara Khachaturian, Zaven Khachaturian, Edward Koo, Lew Kuller, Richard Mohs, Marcelle Morrison- Bogorad, Ronald C. Petersen, Tony Phelps, Judes Poirier, Barry Reisberg, Marwan Sabbagh, David P. Salmon, Mary Sano, Dale Schenk, Lon S. Schneider, James Simpkins, Peter J. Snyder, Stephen Snyder, Ronald G. Thomas, Jacques Touchon, Mark H. Tuszynski, Bruno Veilas, Michael W. Weiner, Richard J. Wurtman. Reporter: Lisa J. Bain, Preventing Dementia: Following in Leon Thal’s Footsteps, Alzheimer’s & Dementia 4: 156-163, 2008. 57. Khachaturian ZS, Snyder PJ, Doody R, Aisen P, Comer M, Dwyer J, Frank RA, Holzapfel A, Khachaturian AS, Korczyn AD, Roses A, Simpkins JW, Schneider LS, Albert MS, Egge R, Deves A, Ferris S, Greenberg BD, Johnson C, Kukull WA, Poirier J, Schenk D, Thies W, Gauthier S, Gilman S, Bernick C, Cummings JL, Fillit H, Grundman M, Kaye J, Mucke L, Reisberg B, Sano M, Pickeral O, Petersen RC, Mohs RC, Carrillo M, Corey-Bloom JP, Foster NL, Jacobsen S, Lee V, Potter WZ, Sabbagh MN, Salmon D, Trojanowski JQ, Wexler N, Bain LJ. A roadmap for the prevention of dementia II: Leon Thal Symposium 2008. Alzheimers Dement 5: 85-92, 2009. PMID 19328434 58. James W. Simpkins, Commentary on “Alzheimer’s disease drug discovery and the problem of the blood-brain barrier”, Alzheimer’s & Dementia 5:433-4, 2009. PMID 19751923 59. Simpkins, J.W., Your aging defense: Biomarkers of oxidative stress, LifeMap Magazine, 1: 10-11, 2010.

Manuscripts Submitted Since Submission of the Application

1. Richardson, TE and JW Simpkins, R- and S-Equol Have Equivalent Cytoprotective Effects in Friedreich’s Ataxia, J of Alternative and Complimentary Medicine, Submitted. 2. James W. Simpkins, Timothy E. Richardson, Sue Yi, Evelyn Perez and D. Covey, Neuroprotection with Non-Feminizing Estrogens, Hormones and Behavior, submitted.

6 3. Timothy E. Richardson, Amanda E. Yu, Yi Wen, Shao-Hua Yang and James W. Simpkins, Estrogen Prevents Oxidative Damage to the Mitochondria in Friedreich’s Ataxia Skin Fibroblasts, Brain Research, Submitted. 4. Wigginton, Jane G. MD; Simpkins, James W. PhD; AbdelFattah , Kareem R. MD; Pepe, Paul E. MD; Gatson, Joshua W. PhD; Warren, Victoria S., RN; Ma, Lisha MD; Martinez, Bobbie J BS; Zang, Qun PhD; Minei, Joseph P. MD; Wigginton, Katharine G.; Maass, David L. BS., Single-Dose, Post-Burn Estrogen Decreases Rodent Burned Skin and Systemic Inflammatory Response for 45 Days Following Severe Burn Injury, Journal of Trauma, Submitted. 5. Yi Wen, Wenjun Li, Roy Gourav, Kun-Lin Jin, James Simpkins, and Shao-Hua Yang, Astroglial PTEN loss disrupts neuronal patterning by dysregulating radial glia-guided neuronal migration, PLoS ONE, submitted. 6. Luedtke RR, E Perez, S-H Yang, R Liu, S Vanveravong, Z Tu, RH. Mach, J W Simpkins, Neuroprotective Effects of Selective, High Affinity Sigma 1 Receptor Antagonists, Brain Research. 7. Poteet, Ethan; Poteet, Ethan; Liu, Ran; Perez E.; Wen, Yi; Simpkins, James; Yang, Shaohua, Protective Effects of Pyruvate Against Zinc-Induced Cytotoxicity in HT-22 Cells. J Neurochemistry, Submitted.

Abstracts Published or Submitted in 2011

1. Richardson TE, SH Yang, Y Wen and JW Simpkins, Estrogen Protection in Friedreich’s Ataxia Skin Fibroblasts, International Congress on Alzheimer’s Disease, Paris July 16- 19, 2011. 2. Sarkar SN and J W Simpkins, Estrogen signaling prevents Aβ-induced defects in dendritic mitochondrial structure and mobility, International Congress on Alzheimer’s Disease, Paris July 16-19, 2011. 3. Wigginton, JG, J W. Gatson, K R AbdelFattah, D L Maass, P E Pepe, and JW Simpkins, Indirect Brain Injury Resulting from Severe Burns Results in Estrogen Reversable Elevations of Markers of Alzheimer's Disease, International Congress on Alzheimer’s Disease, Paris July 16-19, 2011. 4. Wigginton, JG, PE Pepe, KR AbdelFattah, DL Maass, AH Idris, JP Minel, JW Gatson, and JW Simpkins, Indirect brain injury resulting from severe burn results in estrogen reversible elevation of markers of Alzheimer’s disease, American Heart Association, Resuscitation Science Symposium, November 13-15, 2011, Orlando, FL, Abstract #2011-SS-R-17069-AHA. 5. Wigginton, JG, PE Pepe, JW Simpkins, JW Gatson, KG Wigginton, KR AbdelFattah, JP Minel, and DL Maass, Early, single-dose post-burn estrogen significantly decreases burn skin and systemic inflammatory response for 7 days following severe burn injury, AAST Abstract, 2011. 6. Gatson J. …JW Simpkins, Estrone is neuroprotective in rats following traumatic brain injury, American Heart Association, Resuscitation Science Symposium Abstract #18355- AHA.

7 7. Sarkar, S. and JW Simpkins, Estrogen signaling ameliorates soluble A-beta oligomers induced fission and transport, SfN Abstract, Washington, DC, November, 2011. 8. Jun S, Y. Wen, L. Dory and J.W. Simpkins, impaired extracellular superoxide dismutase activity in Alzheimer’s disease mouse model. SfN abstract, Washington, DC, November, 2011. 9. Nixon E and J W Simpkins, Neuroprotective effects of non-feminizing estrogen analogues in retinal neurons, SfN Abstract, Washington, DC, November, 2011. 10. Richardson, TE and J W Simpkins, Estrogen Mechanisms in Friedreich’s Ataxia , SfN Abstract, Washington, DC, November, 2011.

PROJECT 3

Original Publications:

1. Peter Koulen, Christian Madry, R. Scott Duncan, Ji-yeon Hwang, Everett Nixon, Nathalie McClung, Elaine V. Gregg and Meharvan Singh. 2008, Cellular Physiology and Biochemistry, 21:161-172: ‘Progesterone potentiates IP3-mediated calcium signaling through Akt/PKB’ 2. Stanley Stevens, Scott Duncan, Peter Koulen, Laszlo Prokai. 2008, Journal of Proteome Research, in press: ‘Proteomic Analysis of Mouse Brain Microsomes: Identification and Bioinformatic Characterization of Endoplasmic Reticulum Proteins in the Mammalian Central Nervous System’ 3. Volodya Hayrapetyan, Volodymyr Rybalchenko, Nataliya Rybalchenko and Peter Koulen. The cytosolic N-terminus of Presenilin-2 increases single channel activity of brain Ryanodine receptors through direct protein-protein interaction. Cell Calcium, 44(5):507-18. Epub 2008 Apr 25. (2008) PMID: 18440065 4. Ji-yeon Hwang, R. Scott Duncan, Christian Madry, Meharvan Singh, and Peter Koulen. Cell Calcium, 45 (2009), pp. 233-242: ‘Progesterone Potentiates Calcium Release Through IP3 Receptor by an Akt-Mediated Mechanism in Hippocampal Neurons’ DOI information: 10.1016/j.ceca.2008.10.006; PMID: 19081133; NIHMSID # 185286; PMCID: PMC2860454. 5. Rybalchenko V, Grillo MA, Gastinger MJ, Rybalchenko N, Payne AJ, Koulen P. J Recept Signal Transduct Res. 2009 Dec;29(6):326-41: ‘The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca2+‘ PMID: 19899956; NIHMSID # 185326; PMCID: PMC2844704. http://www.pubmedcentral.gov/articlerender.fcgi?artid=2844704 6. R. Scott Duncan, Kent D. Chapman and Peter Koulen. ‘The Neuroprotective Properties of Palmitoylethanolamine Against Oxidative Stress in a Neuronal Cell Line’, Molecular Neurodegeneration, 4:50; 2009; http://www.molecularneurodegeneration.com/content/4/1/50 ; PMID: 20003317; PMCID: PMC2799406. 7. Puja Garg, R. Scott Duncan, Simon Kaja, Peter Koulen. Intracellular Mechanisms of N- Acylethanolamine-Mediated Neuroprotection in Stroke, Neuroscience, 166: 252-262, 2010; Epub ahead of print; http://dx.doi.org/10.1016/j.neuroscience.2009.11.069 PMID: 19963043; PMCID: PMC2830814 8. Aruna Kilaru, Giorgis Isaac, Pam Tamura, David Baxter, R. Scott Duncan, Barney J. Venables, Ruth Welti, Peter Koulen, and Kent D. Chapman Lipid Profiling Reveals Tissue-Specific Differences for Ethanolamide Lipids in Mice Lacking Fatty Acid Amide

8 Hydrolase, Lipids, 2010 Sep;45(9):863-75. Epub 2010 Aug 17. PubMed # 20714818; NIHMSID # 235877; PMCID: PMC2944412 9. Simon Kaja, R. Scott Duncan, Sandra Longoria, Jill D. Hilgenberg, Andrew J. Payne, Neeti M. Desai, Ruby Parikh, Stephanie L. Burroughs, Elaine V. Gregg, Daryl L. Goad, Peter Koulen. Novel mechanism of increased Ca2+ release following oxidative stress in neuronal cells involves type 2 inositol-1,4,5-trisphosphate receptors. Neuroscience. 2010 Nov 11. [Epub ahead of print], in press. PMID: 21075175; doi:10.1016/j.neuroscience.2010.11.010, NIHMS: 253149; PMCID in progress/ submitted 10. Aruna Kilaru, Pamela Tamura, Puja Garg, Giorgis Isaac, David Baxter, R. Scott Duncan, Ruth Welti, Peter Koulen, Kent D. Chapman, and Barney J. Venables. Changes in N- acylethanolamine Pathway Related Metabolites in a Rat Model of Cerebral Ischemia/Reperfusion. Journal of Glycomics & Lipidomics. in press; Research Article J Glycom Lipidom 2010, 1:101; doi: 10.4172/2153-0637.1000101; PMCID in progress/ submitted 11. Puja Garg, R. Scott Duncan, Simon Kaja, Alexander Zabaneh, Kent D. Chapman, Peter Koulen. Lauroylethanolamide and linoleoylethanolamide improve functional outcome in a rodent model for stroke. Neurosci. Lett. in press; 2011; http://dx.doi.org/10.1016/j.neulet.2011.01.073; PMCID in progress/ submitted 12. R. Scott Duncan, Hua Xin, Daryl L. Goad, Kent D. Chapman, Peter Koulen. Protection of Neurons in the Retinal Ganglion Cell Layer against Excitotoxicity by the N- Acylethanolamine, Linoleoylethanolamine. Clinical Ophthalmology 2011;5:543-8. Epub 2011 Apr 26. PMID: 21573043 [PubMed]; PMCID: PMC3090310 13. Simon Kaja, Jill D. Hilgenberg, Volodymyr Rybalchenko, Wanda E. Medina-Ortiz, Elaine V. Gregg, Peter Koulen. Polycystin-2 expression and function in adult mouse lacrimal acinar cells. Invest. Ophthal. & Vis. Sci. 2011 Jul 29;52(8):5605-11. PMID: 21508103. PMCID in progress/ submitted 14. Stephanie L. Burroughs*, R. Scott Duncan*, Parvathi Rayudu, Prasanthi Kandula, Andrew J. Payne, Julie L. Clark, Peter Koulen and Simon Kaja. Plate reader-based assays for measuring cell viability, neuroprotection and calcium in primary neuronal cultures. Journal of Neuroscience Methods, in press; PMID: 21968036; NIHMSID: 328819; PMCID in progress/ submitted

Reviews

15. R.S. Duncan, D.L. Goad, M.A. Grillo, S. Kaja, A.J. Payne, P. Koulen. Control of Intracellular Calcium Signaling as a Neuroprotective Strategy. Molecules 2010, 15(3), 1168-1195; doi:10.3390/molecules15031168; Open access journal: http://www.mdpi.com/1420-3049/15/3/1168/pdf ; NIHMSID # 185364; PMCID: PMC2847496. 16. Simon Kaja, Andrew J. Payne, Stephanie L. Burroughs, Peter Koulen. ‘Homer’ Encyclopedia of Signaling Molecules, Elsevier, in press; 2011; PMCID in progress/ submitted 17. Daryl L. Goad, Michael A. Grillo, Peter Koulen. ‘PKD2’ Encyclopedia of Signaling Molecules, Elsevier,in press; 2011; PMCID in progress/ submitted 18. Michael A. Grillo, Peter Koulen. ‘IRAG’ Encyclopedia of Signaling Molecules, Elsevier, in press; 2011; PMCID in progress/ submitted

Abstracts Submitted or Published in 2011:

9 1. Debra D. Wawro, Shelby Zimmerman, Resonant Sensors Inc. (United States); Robert Magnusson, The Univ. of Texas at Arlington (United States); Peter Koulen, Univ. of Missouri-Kansas City (United States) Paper 8090-25 ‘Optics nanotechnology enables rapid label-free diagnostics for biomedical applications’. SPIE/OSA European Conference on Biomedical Optics, meeting abstracts. 2011 2. S. KAJA, P. GARG, P. KOULEN. ‘Novel mouse model for sporadic Alzheimer's Disease. Society for Neuroscience 41st Annual Meeting, 2011. Washington, DC.

CORE B (from previous period of funding)

1. Stanley Stevens, Scott Duncan, Peter Koulen, Laszlo Prokai. 2008, Journal of Proteome Research, in press: ‘Proteomic Analysis of Mouse Brain Microsomes: Identification and Bioinformatic Characterization of Endoplasmic Reticulum Proteins in the Mammalian Central Nervous System’ 2. Prokai-Tatrai K, Perjesi P, Rivera-Portalatin NM, Simpkins JW , Prokai L., Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. Steroids 73: 280-288, 2008. 3. Prokai, L., K. Prokai-Tatrai, P. Perjesi and J. W. Simpkins, Mechanistic insights into the direct antioxidant effects of estrogens, Drug Development Research, In Press, 2008. 4. Prokai-Tatrai, K., L. Prokai, James W. Simpkins and Marianna E. Jung, Phenolic compounds protect cultured hippocampal neurons against ethanol-induced oxidative stress, Int. J. Mol. Sci. 10: 1773-1787, 2009. PMCID - PMC2680646 5. Prokai L, Stevens SM Jr, Rauniyar N, Nguyen V. Rapid label-free identification of estrogen- induced differential protein expression in vivo from mouse brain and uterine tissue. J. Proteome Res. 2009; 8: 3862–3872. PMID: 19545149 6. Prokai-Tatrai K, Bonds D, Prokai L. Simultaneous measurement of 17b-estradiol, 17a- estradiol and estrone by GC-isotope dilution MS/MS. Chromatographia 2010; 71: 311–315. PMID: Pending 7. Braden BB, Talboom JS, Crain ID, Simard AR, Lukas RJ, Prokai L, Scheldrup MR, Bowman BL, Bimonte-Nelson HA. Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats. Neurobiol. Learn. Mem. 2010; 93: 444–453. PMID: 20074654