Biochemical Principles Clinical Dimensions of Biochemisry

 Final Project and Paper

For your final project and paper: Select a topic that interests you. You can work individually or in a group. You will present your research in class and in writing, in a format to be determined.  The following is a partial list of references you can draw from. Most of them are available at the main desk of the Science Library, on the table to the left just after you enter. Feel free to discuss your research with us. Details will follow.

Partial List of References for Clinical Dimensions Part of Biochemical Principles 330

Chen Z-Y, Jing D, Bath KG, Ieraci A, Khan T, et al. 2006. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314:140-3

Du J, McEwen BS, Manji HK. 2009a. Glucocorticoid receptors modulate mitochondrial function. Commun. & Integr. Biol. 2:1-3

Du J, Wang Y, Hunter R, Wei Y, Blumenthal R, et al. 2009b. Dynamic regulation of mitochondrial function by glucocorticoids. Proc. Natl. Acad. Sci. USA 106:3543-8

Francis D, Diorio J, Liu D, Meaney MJ. 1999. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155-8

Gianaros PJ, Horenstein JA, Hariri AR, Sheu LK, Manuck SB, et al. 2008. Potential neural embedding of parental social standing. Soc Cogn Affect Neurosci 3:91-6

Hill MN, Karatsoreos IN, Hillard CJ, McEwen BS. 2010. Rapid elevations in limbic endocannabinoid content by glucocorticoid hormones in vivo. Psychoneuroendocrinology 35:1333-8

Hill MN, McEwen BS. 2009. Endocannabinoids: The silent partner of glucocorticoids in the synapse. Proc. Natl. Acad. Sci. USA 106:4579-80

Hunter RG, Bellani R, Bloss E, costa A, Romeo RD, McEwen BS. 2007. Regulation of CART mRNA by stress and corticosteroids in the hippocampus and amygdala. Brain Res. 1152:234-40

Joels M. 2006. Corticosteroid effects in the brain: U-shape it. Trends Pharmacol. Sci. 27:244-50

Joels M, Pu Z, Wiegert O, Oitzl MS, Krugers HJ. 2006. Learning under stress: how does it work? Trends Cogn. Sci.

Johnson LR, Farb C, Morrison JH, McEwen BS, LeDoux JE. 2005. Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala. Neuroscience 136:289-99

Karst H, Berger S, Turiault M, Tronche F, Schutz G, Joels M. 2005. Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone. Proc. Natl. Acad. Sci. USA 102:19204-7

Kaufman D, Banerji MA, Shorman I, Smith ELP, Coplan JD, et al. 2007. Early-life stress and the development of obesity and insulin resistance in juvenile bonnet macaques. Diabetes 56:1-5

Kaufman D, Smith ELP, Gohil BC, Banerji MA, Coplan JD, et al. 2005. Early appearance of the metabolic syndrome in socially reared bonnet macaques. J. Clin. Endocrin. & Metab. 90:404-8

Maccari S, Morley-Fletcher S. 2007. Effects of prenatal restraint stress on the hypothalamus-pituitary-adrenal axis and related behavioural and neurobiological alterations. Psychoneuroendo. 32:S10-S5

Moutsatsou P, Psarra A-MG, Tsiapara A, Paraskevakou H, Davaris P, Sekeris CE. 2001. Localization of the glucocorticoid receptor in rat brain mitochondria. Arch. Biochem. Biophys. 386:69-78

Munhoz CD, Sorrells SF, Caso JR, Scavone C, Sapolsky RM. 2010. Glucocorticoids exacerbate lipopolysaccharide-induced signaling in the frontal cortex and hippocampus in a dose-dependent manner. J Neurosci 30:13690-8

Okuda S, Roozendaal B, McGaugh JL. 2004. Glucocorticoid effects on object recognition memory require training-associated emotional arousal. Proc. Natl. Acad. Sci. USA 101:853-8

Poulton R, Caspi A, Milne BJ, Thomson WM, Taylor A, et al. 2002. Association between children's experience of socioeconomic disadvantage and adult health: a life-course study. The Lancet 360:1640-5

Prager EM, Johnson LR. 2009. Stress at the synapse: signal transduction mechanisms of adrenal steroids at neuronal membranes. Sci Signal 2:re5

Quan N, Avitsur R, Stark JL, He L, Lai W, et al. 2003. Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice. J. Neuroimmunol. 137:51-8

Sapolsky RM, Romero LM, Munck AU. 2000. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Rev. 21:55-89

Soliman F, Glatt CE, Bath KG, Levita L, Jones RM, et al. 2010. A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science 327:863-6

Tasker JG, Di S, Malcher-Lopes R. 2006. Minireview: Rapid glucocorticoid signaling via membrane-associated receptors. Endocrinology 147:5549-56

Tottenham N, Hare TA, Quinn BT, McCarry TW, Nurse M, et al. 2010. Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev Sci 13:46-61

Venero C, Borrell J. 1999. Rapid glucocorticoid effects on excitatory amino acid levels in the hippocampus: a microdialysis study in freely moving rats. Eur. J. Neurosci. 1:2465-73

Wakschlak A, Weinstock M. 1990. Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress. Physiol. Behav. 48:289-92

McEwen BS. Protective and damaging effects of stress mediators. N Engl

J Med. 1998;338:171-179.

Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence

stress responses? Integrating permissive, suppressive, stimulatory, and

preparative actions. Endocr Rev. 2000;21:55-89.

Hariri AR, Goldberg TE, Mattay VS, et al. Brain-derived neurotrophic factor

val66 met polymorphism affects human memory-related hippocampal

activity and predicts memory performance. J Neurosci. 2003;23:6690-6694.

McEwen BS. Protective and damaging effects of stress mediators.

N Engl J Med 338: 171–179, 1998.

McEwen BS. Stress and hippocampal plasticity. Annu Rev Neurosci

22: 105–122, 1999.

McEwen BS, Wingfield JC. The concept of allostasis in biology

and biomedicine. Horm Behav 43: 2–15, 2003

Jack P. Shonkoff, W. Thomas Boyce, Bruce S. McEwen.   Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities: Building a New Framework for Health Promotion and Disease Prevention. JAMA. 2009;301(21):2252-2259

Barker DJ. The fetal and infant origins of adult

disease. BMJ. 1990;301(6761):1111.

Anda RF, Felitti VJ, Bremner JD, et al. The enduring

effects of abuse and related adverse experiences in childhood: a convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin

Neurosci. 2006;256(3):174-186.

 Hillis SD, Anda RF, Dube SR, Felitti VJ, Marchbanks

PA, Marks JS. The association between adverse childhood

experiences and adolescent pregnancy, longterm

psychosocial consequences, and fetal death.

Pediatrics. 2004;113(2):320-327.

Geronimus AT, Hicken M, Keene D, Bound J.

“Weathering” and age patterns of allostatic load scores

among blacks and whites in the United States. Am J

Public Health. 2006;96(5):826-833.

Cacioppo, J Genome Biology(Vol 8 No R189)and  Proceedings of the National Academy of Sciences (PNAS Vol. 108, No. 7): gene activity, immune systems and loneliness

Miller, G. Cole, S. immune systems and SES

Lutgendorf, S social circumstances and gene expression in cancer

Harrell, CJP et al(2011) Multiple Pathways Linking Racism to Health Outcomes, Dubois Review: Social Sciences Research on Race- summarizes evidence pointing to psychophysiologcal pathways linking facets of racist environments to disease pathways.

Geronimus, A (2010) Do US Black Women Experience Accelerated Biological Aging? Human Nature: An Interdisciplinary Biological Perspective 21(1): 19-38

In our evening sessions, we will meet to discuss papers that bring together our abstract concepts from class with applied concepts from the clinical literature.  Our leading paper and the first one we will read is a landmark study in 1998 called the ACE study in which the health status of 20,000 patients was correlated with childhood stress.  As the semester progresses, we will move from structure to metabolism, illuminating how every aspect of biochemistry can be dysregulated by chronic stress.

Doctor Aronson and Professor O'Hara will in general assign a paper a week in advance (whenever possible) and will expect participation in an on-line group discussion prior to the Thursday evening sessions.  Evening sessions will pick up threads from the on-line discussions.

You will all be asked to post an original comment AND to respond to another student's comment. Each student's comment should have at least one response before you start a threaded discussion.

Below are some guidelines for your original comments and responses to your classmates comments. 

Guidelines for Response:  Pick out some aspect of the paper that you find especially notable.  What we will especially appreciate when possible are those comments that relate back to material we are studying in lecture. Your comment should be no more than 100 words and should be posted by 8 AM Tuesday

Guidelines for Comment on a Peer's Response:  The length of your  response is up to you. The purpose is to “listen” to each other and learn from each other through respect, reflection, integration, and critical thinking. In your response, do one or more of the following:

• Ask a thoughtful question.
• Comment on what particularly interested you: what particularly resonated with you, expanded your understanding, inspired you, and so on. Be very specific.   (The best way to do this is to copy the part of the student’s  you are commenting on, and paste it into your text before your own comments.  That way we can all see what you are talking about.)
• Disagree respectfully on something your classmate wrote, and explain why you feel the way you do. Be specific.

You are welcome to comment on other responses as well, but this optional. Your response will be due by 8 AM on Thursday morning so that we can read all comments and responses by 8 PM.