Behavioral pathology induced by repeated systemic injections of 3-nitropropionic acid mimics the motoric symptoms of Huntington's disease

Borlongan, Cesario V.; Koutouzis, Theodore K.; Freeman, Thomas B.; Cahill, David W.; Sanberg, Paul R.

doi:10.1016/0006-8993(95)00901-2

Cited by 116 publications

(49 citation statements)

References 17 publications

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“…Several animal models for HD have been described, including lesions of the striatum induced by excitotoxins (e.g., quinolinic acid) and metabolic poisons (e.g., 3-nitropropionic acid). These models show striatal pathology similar to that seen in H D (Coyle and Schwarcz, 1976;McGreer and McGreer, 1976;Beal et al, 1986Beal et al, , 1993Bossi et al, 1993;Brouillet et al, 1993Brouillet et al, , 1995, and also replicate some of the motor and cognitive symptoms of the disease (Borlongan et al, 1995;Brouillet et al, 1995;Furtado and Mazurek, 1996;Palfi et al, 1996;Emerich et al, 1997;Kodsi and Swerdlow, 1997;Shear et al, 1998a,b). However, a major disadvantage of these neurotoxic models is that they lack the genetic pathogenesis and the progressive nature of HD.…”

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confidence: 72%

Selective Discrimination Learning Impairments in Mice Expressing the Human Huntington's Disease Mutation

Lione

Carter²,

Hunt³

et al. 1999

J. Neurosci.

355

241

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Cognitive decline is apparent in the early stages of Huntington's disease and progressively worsens throughout the course of the disease. Expression of the human Huntington's disease mutation in mice (R6/2 line) causes a progressive neurological phenotype with motor symptoms resembling those seen in Huntington's disease. Here we describe the cognitive performance of R6/2 mice using four different tests (Morris water maze, visual cliff avoidance, two-choice swim tank, and T-maze). Behavioral testing was performed on R6/2 transgenic mice and their wild-type littermates between 3 and 14.5 weeks of age, using separate groups of mice for each test. R6/2 mice did not show an overt motor phenotype until ∼8 weeks of age. However, between 3.5 and 8 weeks of age, R6/2 mice displayed progressive deterioration in specific aspects of learning in the Morris water maze, visual cliff, two-choice swim tank, and T-maze tasks. The age of onset and progression of the deficits in the individual tasks differed depending on the particular task demands. Thus, as seen in humans with Huntington's disease, R6/2 mice develop progressive learning impairments on cognitive tasks sensitive to frontostriatal and hippocampal function. We suggest that R6/2 mice provide not only a model for studying cognitive and motor changes in trinucleotide repeat disorders, but also a framework within which the functional efficacy of therapeutic strategies aimed at treating such diseases can be tested.

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mentioning

confidence: 72%

Selective Discrimination Learning Impairments in Mice Expressing the Human Huntington's Disease Mutation

Lione

Carter²,

Hunt³

et al. 1999

J. Neurosci.

355

241

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“…In non-human primates with chronic 3-NP treatment, a variety of abnormal movements are highly reminiscent to those seen in HD patients; these types of movements have never been observed in rats in the same experimental conditions. As discussed earlier, rats chronically treated with 3-NP did not show clearly identifiable dyskinetic movements resembling chorea even though hyperlocomotor activity has been reported early in the course of intoxication, as well as the presence of dystonia, bradykinesia and gait abnormalities [46,49] . Therefore, it may be that the dyskinetic component of HD symptomatology is part of a motor repertoire that can only be expressed in primates.…”

Section: In Vivo and In Vitro Models Of Hdmentioning

confidence: 71%

“…Initially, systemically 3-NP-treated animals exhibited significant hyperactivity during the first 2 injections, reaching a plateau after the third injection, and then displaying hypoactivity after the fourth injection [52] . The study by Mettler indicates that small lesions are visible at the onset of hypoactivity, but at the end of the long-term course of 3-NP administration, larger lesions were noted; there is no visible striatal degeneration at the period of hyperactivity [53][54][55] . Despite chronic 3-NP rat models replicating some of the features of HD, this model still has some limitations.…”

Section: In Vivo and In Vitro Models Of Hdmentioning

confidence: 99%

“…Behavioral studies with the chronic 3-NP model indicated that the HD-like striatal lesions were also associated with symptoms and persistent abnormal movements, in many ways analogous to HD motor deficits. In a study performed in animals repeatedly treated with 3-NP (10 mg·kg -1 every 4 d for 28 d), a quantitative analysis of spontaneous locomotor behavior showed that this protocol was associated with an early phase of hyperkinesia (first and second week of treatment), followed by a later phase of hypokinesia [49,50] . The animals subjected to the chronic 3-NP intoxication always displayed bilateral and symmetrical dorso-lateral striatal lesions.…”

Section: In Vivo and In Vitro Models Of Hdmentioning

confidence: 99%

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Animal models of Huntington's disease: implications in uncovering pathogenic mechanisms and developing therapies

Wang

Qin

2006

Acta Pharmacologica Sinica

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Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, which is caused by an abnormal expansion of Cytosine Adenine Guanine (CAG) trinucleotide repeat in the gene making huntingtin (Htt). Despite intensive research efforts devoted to investigate molecular mechanisms of pathogenesis, effective therapy for this devastating disease is still not available at present. The development of various animal models of HD has offered alternative approaches in the study of HD molecular pathology. Many HD models, including chemicalinduced models and genetic models, mimic some aspects of HD symptoms and pathology. To date, however, there is no ideal model which replicates all of the essential features of neuropathology and progressive motor and cognitive impairments of human HD. As a result, our understanding of molecular mechanisms of pathogenesis in HD is still limited. A new model is needed in order to uncover the pathogenesis and to develop novel therapies for HD. In this review we discussed usefulness and limitations of various animal and cellular models of HD in uncovering molecular mechanisms of pathogenesis and developing novel therapies for HD.

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“…Animal models that closely mimic the neurobiological and clinical symptoms of the disease can be used to test experimental treatments for HD across different stages of the disease [71,84].…”

confidence: 99%

Review: structure of amyloid fibril in diseases

Ghahghaei¹,

Faridi²

2009

JBiSE

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Tissue deposition of normally soluble proteins, or their fragments, as insoluble amyloid fibrils causes both acquired and hereditary systemic amyloidoses, which is usually fatal. Amyloid is associated with serious diseases such as Alzheimer's disease, type 2 diabetes, Parkinson's Disease, Huntington's Disease, cancer and the transmissible spongiform encephalopathies. Information concerning the structure and mechanism of formation of fibrils in these diseases is critical for understanding the process of pathology of the amyloidoses and to the development of more effective therapeutic agents that target the underlying disease mechanisms. Structural models have been made using information from a wide variety of techniques, including electron microscopy, X-ray diffraction, solid state NMR, and Congo red and CD spectroscopy. Although each type of amyloidosis is characterised by a specific amyloid fibril protein, the deposits share pathognomonic histochemical properties and the structural morphology of all amyloid fibrils is very similar. In fact, the structural similarity that defines amyloid fibres exists principally at the level of β-sheet folding of the polypeptides within the protofilament, while the different types vary in the supramolecular assembly of their protofilaments.

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Behavioral pathology induced by repeated systemic injections of 3-nitropropionic acid mimics the motoric symptoms of Huntington's disease

Cited by 116 publications

References 17 publications

Selective Discrimination Learning Impairments in Mice Expressing the Human Huntington's Disease Mutation

Selective Discrimination Learning Impairments in Mice Expressing the Human Huntington's Disease Mutation

Animal models of Huntington's disease: implications in uncovering pathogenic mechanisms and developing therapies

Review: structure of amyloid fibril in diseases

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