Abstract

The goals are to clarify the genetics and neurobiology of Huntington's Disease. These goals will be accomplished through administrative and clinical cores which will facilitate collaborations and maintain a well-characterized research population.
The aims of the project are to predict the risk of H.D. in at-risk individuals; to use recombinant DNA and restriction enzyme techniques to investigate linkage in large families available in Maryland in order to study genetic heterogeneity in H.D.; to study receptor abnormalities in H.D. with positron emission tomography and to relate these abnormalities to studies of the neuropsychology of memory and attention, and to abnormalities of eye movements. Post-mortem material from clinically well studied cases will be used to develop a quantitative neuropathology of H.D. using autoradiographic techniques, studies of the GABA-benzodiazepine receptors and measurement of glutamate and related acidic analogs in the brains of H.D. patients. The function of the primate neustriatum will be studied in behaving primates and will be related to striatal inhomogeneities. Results of this research will clarify the pathogenetic mechanisms in order to formulate hypotheses for a rationale treatment and preventative measures for this tragic disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS016375-08
Application #
3099631
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1980-07-01
Project End
1990-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Faria, Andreia V; Ratnanather, J Tilak; Tward, Daniel J et al. (2016) Linking white matter and deep gray matter alterations in premanifest Huntington disease. Neuroimage Clin 11:450-460
Krause, Amanda; Mitchell, Claire; Essop, Fahmida et al. (2015) Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. Am J Med Genet B Neuropsychiatr Genet 168:573-85
Ross, Christopher A; Pantelyat, Alex; Kogan, Jane et al. (2014) Determinants of functional disability in Huntington's disease: role of cognitive and motor dysfunction. Mov Disord 29:1351-8
Hua, Jun; Unschuld, Paul G; Margolis, Russell L et al. (2014) Elevated arteriolar cerebral blood volume in prodromal Huntington's disease. Mov Disord 29:396-401
Unschuld, Paul G; Liu, Xinyang; Shanahan, Megan et al. (2013) Prefrontal executive function associated coupling relates to Huntington's disease stage. Cortex 49:2661-73
Nucifora, Leslie G; Burke, Kathleen A; Feng, Xia et al. (2012) Identification of novel potentially toxic oligomers formed in vitro from mammalian-derived expanded huntingtin exon-1 protein. J Biol Chem 287:16017-28
Jiang, Mali; Wang, Jiawei; Fu, Jinrong et al. (2012) Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat Med 18:153-8
Biglan, K M; Dorsey, E R; Evans, R V V et al. (2012) Plasma 8-hydroxy-2'-deoxyguanosine Levels in Huntington Disease and Healthy Controls Treated with Coenzyme Q10. J Huntingtons Dis 1:65-9
Unschuld, Paul G; Joel, Suresh E; Liu, Xinyang et al. (2012) Impaired cortico-striatal functional connectivity in prodromal Huntington's Disease. Neurosci Lett 514:204-9
Unschuld, Paul G; Joel, Suresh E; Pekar, James J et al. (2012) Depressive symptoms in prodromal Huntington's Disease correlate with Stroop-interference related functional connectivity in the ventromedial prefrontal cortex. Psychiatry Res 203:166-74

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