A Comprehensive Comparison Powerpoint

Jennifer K. OcasioBiol. 3095-142

A Comprehensive Comparison of the Motor and Behavioral

Symptoms of Adult-Onset and Juvenile Huntington’s Disease

George HuntingtonGreek word choreiaExcessive repetition of CAG on chromosome 4Normal: less than 25Unaffected Huntington’s: 25-35Adult-Onset: 36-40Juvenile: more than 40

Introduction

CAG repetitions in chromosome 4Produces mutant huntingtin

Neurodegeneration of the striatumCharacteristic involuntary movements

ChoreaBehavioral abnormalities

Common Aspects

On the left is a section of an HD brain demonstrating the damage to the striatum. On the right is the brain of a normal person

Unaffected brain with neurons and no inflammation

Neurodegeneration of the striatum caused by Huntington’s disease. There are few neurons left and reactive gliosis (neuroinflammation)

CAG repetitionsGraeme et al. yeast artificial

chromosome miceElectrophysiological abnormalitiesCytoplasmic toxicityBehavioral abnormalities

Rapid circlingConfusion

Prevalent Differences

Laforet et al. transgenic miceGaitHyperactivity levelsBalanceClaspingDisorientation

Prevalent Differences

Concentration of mutant huntingtinAutismLearning problemsSpasticityPsychological problems

Prevalent Differences

4 to 8 per 100,000 people have HD

5 to 10% are Juvenile cases

Dominant hereditary disorder

Conclusion

Aronin N, Chase K, Young C, Sapp E, Schwarz C, Matta N, Kornreich R, Lanwehrmeyer B, Bird E, Beal M,

Vonsattel J, Smith T, Carraway R, Boyce F, Young A, Penney J and DiFiglia M. 1995. CAG expansion

affects the expression of mutant huntingtin in the Huntington's disease brain. Neur. 15(5):1193-1201.

Carter R, Lione L, Humby T, Mangiarini L, Mahal A, Bates G, Dunnett S and Morton J. 1999.

Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington’s Disease

Mutation. J Neurosci. 19(8):3248–3257

Graeme J, Agopyan N, Gutekunst C, Leavitt B, LePiane F, Singaraja R, Smith D, Bissada N, McCutcheon

K, Nasir J, Jamot L, Li X, Stevens M, Rosemond E, Roder J, Phillips A, Rubin E, Hersch S, and Hayden M.

1999. A YAC Mouse Model for Huntington's Disease with Full-Length Mutant Huntingtin, Cytoplasmic

Toxicity, and Selective Striatal Neurodegeneration. Neur. 23(1):181-192.

References

Harper PS, Lim C and Craufurt D. 2000. Ten years of presymptomatic testing for Huntington's disease:

the experience of the UK Huntington's Disease Prediction Consortium. J Med Genet. 37(8):567-571.

Huntington G. 2003. On Chorea. J Neuropsych Clin Neurosci. 15:109-112.

Laforet G, Sapp E, Chase K, McIntyre C, Boyce F, Campbell M, Cadigan B, Warzecki L, Tagle D,

Hemachandra P, Cepeda C, Calvert C, Jokel E, Klapstein G, Ariano M, Levine M, DiFiglia M, and

Aronin N. 2001. Changes in Cortical and Striatal Neurons Predict Behavioral and Electrophysiological

Abnormalities in a Transgenic Murine Model of Huntington’s Disease. J Neurosci, 21(23):9112–9123.

Montoya A, Price BH, Menear M and Lepage M. 2006. Brain imaging and cognitive dysfunctions in

Huntington's disease. J Psych Neurosci. 31(1):21-9.

References

National Institute of Neurological Disorders and Stroke. 2009. Huntington's Disease: Hope Through

Research. <http://www.ninds.nih.gov/disorders/huntington/detail_ huntington.htm#135523137> Accessed

2009 Sep 13.

National Research Roster for Huntington Disease Patients & Families. 2004. The Brain & HD. <

http://hdroster.iu.edu/AboutHD/brainAndHD.asp> Accessed 2009 Dec 4.

Revilla FJ and Grutzendler J. 2008. Huntington Disease. Huntington Disease: eMedicine Neurology. <

http://emedicine.medscape.com/article/1150165-overview> Accessed 2009 Sep 13.

Squitieri F, Frati L, Ciarmiello A, Lastoria S and Quarrell O. 2006. Juvenile Huntington's disease: Does a dosage-effect pathogenic mechanism differ from the classical adult disease? Mech Age Devel. 127(2):208-212

References