Chapter title |
The Use of Perinatal 6-Hydroxydopamine to Produce a Rodent Model of Lesch–Nyhan Disease
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Chapter number | 444 |
Book title |
Neurotoxin Modeling of Brain Disorders — Life-long Outcomes in Behavioral Teratology
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Published in |
Current topics in behavioral neurosciences, April 2016
|
DOI | 10.1007/7854_2016_444 |
Pubmed ID | |
Book ISBNs |
978-3-31-934134-7, 978-3-31-934136-1
|
Authors |
Knapp, Darin J, Breese, George R, Darin J. Knapp, George R. Breese, Knapp, Darin J., Breese, George R. |
Abstract |
Lesch-Nyhan disease is a neurologically, metabolically, and behaviorally devastating condition that has eluded complete characterization and adequate treatment. While it is known that the disease is intimately associated with dysfunction of the hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene that codes for an enzyme of purine metabolism (hypoxanthine-guanine phosphoribosyltransferase) and is associated with neurological, behavioral, as well as metabolic dysfunction, the mechanisms of the neurobehavioral manifestations are as yet unclear. However, discoveries over the past few decades not only have created useful novel animal models (e.g., the HPRT-deficient mouse and the serendipitously discovered perinatal 6-hydroxydopamine (6-OHDA lesion model), but also have expanded into epigenetic, genomic, and proteomic approaches to better understand the mechanisms underlying this disease. The perinatal 6-OHDA model, in addition to modeling self-injury and dopamine depletion in the clinical condition, also underscores the profound importance of development in the differential course of maladaptive progression in the face of a common/single neurotoxic insult at different ages. Recent developments from clinical and basic science efforts attest to the fact that while the disease would seem to have a simple single gene defect at its core, the manifestations of this defect are profound and unexpectedly diverse. Future efforts employing the 6-OHDA model and others in the context of the novel technologies of genome editing, chemo- and opto-genetics, epigenetics, and further studies on the mechanisms of stress-induced maladaptations in brain all hold promise in taking our understanding of this disease to the next level. |
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France | 1 | 33% |
United States | 1 | 33% |
Unknown | 1 | 33% |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
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Unknown | 22 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 4 | 18% |
Student > Doctoral Student | 3 | 14% |
Other | 2 | 9% |
Lecturer | 1 | 5% |
Professor | 1 | 5% |
Other | 3 | 14% |
Unknown | 8 | 36% |
Readers by discipline | Count | As % |
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Psychology | 3 | 14% |
Medicine and Dentistry | 2 | 9% |
Biochemistry, Genetics and Molecular Biology | 2 | 9% |
Unspecified | 1 | 5% |
Other | 2 | 9% |
Unknown | 8 | 36% |