Skip to main content

Animal Models of Huntington’s Disease

  • Chapter
  • First Online:
Animal Models of Neurological Disorders

Abstract

Huntington’s disease (HD) is an autosomal dominant, hyperkinetic movement disorder, and progressive neurodegenerative disorder characterized by choreiform abnormal movements, cognitive deficits, psychiatric manifestations, emotional disturbances, and dementia associated with progressive striatal atrophy. The disorder was first described in 1872 by Dr. George Huntington in his article titled “On Chorea.” Dr. Huntington entitled the disease “Hereditary Chorea,” whereas observations of some cases which do not present with chorea later led to the acceptance of the “Huntington’s Disease” label. The HD gene (IT15) is sited on the short arm of chromosome 4, and the normal number of CAG (glutamine) repeats is expanded (generally >40). Genetic mutation in HD gene results in an expanded polyglutamine stretch in the NH2 terminus of huntingtin protein (HTT).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Borlongan C, Koutouzis T, Randall T et al (1995) Systemic 3-nitropropionic acid: behavioral deficits and striatal damage in adult rats. Brain Res Bull 36:549–556

    Article  CAS  PubMed  Google Scholar 

  • Brouillet E, Hantraye P, Ferrante R et al (1995) Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci 92:7105–7109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coyle JT, Schwarcz R (1976) Lesion of striatal neurons with kainic acid provides a model for Huntington’s chorea

    Google Scholar 

  • Dautry C, Vaufrey F, Brouillet E et al (2000) Early N-acetylaspartate depletion is a marker of neuronal dysfunction in rats and primates chronically treated with the mitochondrial toxin 3-nitropropionic acid. J Cereb Blood Flow Metab 20:789–799

    Article  CAS  PubMed  Google Scholar 

  • Ferrante R, Kowall N, Cipolloni P et al (1993) Excitotoxin lesions in primates as a model for Huntington’s disease: histopathologic and neurochemical characterization. Exp Neurol 119:46–71

    Article  CAS  PubMed  Google Scholar 

  • Gould D, Gustine D (1982) Basal ganglia degeneration, myelin alterations, and enzyme inhibition induced in mice by the plant toxin 3-nitropropanoic acid. Neuropathol Appl Neurobiol 8:377–393

    Article  CAS  PubMed  Google Scholar 

  • Guyot M, Hantraye P, Dolan R et al (1997) Quantifiable bradykinesia, gait abnormalities and Huntington’s disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid. Neuroscience 79:45–56

    Article  CAS  PubMed  Google Scholar 

  • Hamilton B, Gould D (1987) Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: a type of hypoxic (energy deficient) brain damage. Acta Neuropathol 72:286–297

    Article  CAS  PubMed  Google Scholar 

  • Jang M, Lee M, Cho I (2014) Ethyl pyruvate ameliorates 3-nitropropionic acid-induced striatal toxicity through anti-neuronal cell death and anti-inflammatory mechanisms. Brain Behav Immun 38:151–165

    Article  CAS  PubMed  Google Scholar 

  • Kalonia H, Kumar P, Kumar A et al (2010a) Protective effect of montelukast against quinolinic acid/malonic acid induced neurotoxicity: possible behavioral, biochemical, mitochondrial and tumor necrosis factor-α level alterations in rats. Neuroscience 171:284–299

    Article  CAS  PubMed  Google Scholar 

  • Kalonia H, Kumar P, Kumar A et al (2010b) Protective effect of rofecoxib and nimesulide against intra-striatal quinolinic acid-induced behavioral, oxidative stress and mitochondrial dysfunctions in rats. Neurotoxicology 31:195–203

    Article  CAS  PubMed  Google Scholar 

  • Kalonia H, Kumar P, Kumar A (2011) Attenuation of proinflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington like alterations in rats. Brain Res 1372:115–126

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Sharma N, Mishra J et al (2013) Synergistical neuroprotection of rofecoxib and statins against malonic acid induced Huntington’s disease like symptoms and related cognitive dysfunction in rats. Eur J Pharmacol 709:1–12

    Article  CAS  PubMed  Google Scholar 

  • Kumar P, Kumar A (2009) Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: a novel nitric oxide mechanism. Food Chem Toxicol 47:2522–2530

    Article  CAS  PubMed  Google Scholar 

  • Mishra J, Kumar A (2014) Improvement of mitochondrial NAD+/FAD+-linked state-3 respiration by caffeine attenuates quinolinic acid induced motor impairment in rats: Implications in Huntington’s disease. Pharmacol Rep 66:1148–1155

    Article  CAS  PubMed  Google Scholar 

  • Nishino H, Kumazaki M, Fukuda A et al (1997) Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death and dysfunction of the blood-brain barrier: involvement of dopamine toxicity. Neurosci Res 27:343–355

    Article  CAS  PubMed  Google Scholar 

  • Palfi S, Ferrante RJ, Brouillet E, Beal MF, Dolan R, Guyot MC, Peschanski M, Hantraye P (1996) Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington’s disease. J Neurosci 16(9):3019–3025

    CAS  PubMed  Google Scholar 

  • Park J, Lee S, Chu K et al (2008) Galantamine reduces striatal degeneration in 3-nitropropionic acid model of Huntington’s disease. Neurosci Lett 448:143–147

    Article  CAS  PubMed  Google Scholar 

  • Pérez-De La Cruz V, Elinos-Calderón D, Robledo-Arratia Y et al (2009) Targeting oxidative/nitrergic stress ameliorates motor impairment, and attenuates synaptic mitochondrial dysfunction and lipid peroxidation in two models of Huntington’s disease. Behav Brain Res 199:210–217

    Article  PubMed  Google Scholar 

  • Pintor A, Tebano M, Martire A et al (2006) The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum. Neuropharmacology 51:1004–1012

    Article  CAS  PubMed  Google Scholar 

  • Sagredo O, González S, Aroyo I et al (2009) Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease. Glia 57:1154–1167

    Article  PubMed  PubMed Central  Google Scholar 

  • Szabo A, Papp A, Nagymajtényi L (2005) Effects of 3-nitropropionic acid in rats: general toxicity and functional neurotoxicity. Ar Hig Rada Toksikol 56:297–302

    CAS  Google Scholar 

  • Toulmond S, Tang K, Bureau Y et al (2004) Neuroprotective effects of M826, a reversible caspase-3 inhibitor, in the rat malonate model of Huntington’s disease. Br J Pharmacol 141:689–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valdeolivas S, Pazos M, Bisogno T et al (2013) The inhibition of 2-arachidonoyl-glycerol (2-AG) biosynthesis, rather than enhancing striatal damage, protects striatal neurons from malonate-induced death: a potential role of cyclooxygenase-2-dependent metabolism of 2-AG. Cell Death Dis 4:862

    Article  Google Scholar 

  • Valdeolivas S, Satta V, Pertwee R et al (2012) Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington’s disease: role of CB1 and CB2 receptors. ACS Chem Neurosci 3:400–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilhelm E, Jesse C, Bortolatto C et al (2013) Correlations between behavioural and oxidative parameters in a rat quinolinic acid model of Huntington’s disease: protective effect of melatonin. Eur J Pharmacol 701:65–72

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Puneet Kumar Bansal .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kaur, N., Jamwal, S., Kaur Gill, H., Bansal, P.K. (2017). Animal Models of Huntington’s Disease. In: Bansal, P., Deshmukh, R. (eds) Animal Models of Neurological Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-10-5981-0_4

Download citation

Publish with us

Policies and ethics