title: Cellular and subcellular localization of Huntingtin [corrected] aggregates in the brain of a rat transgenic for Huntington disease.
abstract: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by emotional, cognitive, and motor dysfunctions. Aggregation of huntingtin is a hallmark of HD and, therefore, a crucial parameter for the evaluation of HD animal models. We investigated here the regional, cellular, and subcellular distribution of N-terminal huntingtin aggregates and associated neuropathological changes in the forebrain of a rat transgenic for HD (tgHD). The tgHD rat brain showed enormously enlarged lateral ventricles and a similar atrophy of cortical and subcortical areas as known in HD patients. Huntingtin aggregates of varying size and forms were regionally identified in neuronal nuclei, cytoplasm, dendrites, dendritic spines, axons, and synaptic terminals, closely resembling the results described earlier for human HD brains and in established HD mouse models. Huntingtin aggregates in mitochondria support mitochondrial dysfunction as contributing to the disease pathogenesis. Dark cell degeneration was reminiscent of results in HD individuals and HD mouse models. Interestingly, huntingtin aggregates were especially well accumulated in two interacting limbic forebrain systems, the ventral striatopallidum and the extended amygdala, which may contribute to the early onset of emotional changes observed in the tgHD rat. In conclusion, the tgHD rat model reflects to a remarkable extent the cellular and subcellular neuropathological key features as observed in human HD and HD mouse brains and hints of changes in limbic forebrain systems, which may elucidate the emotional dysfunction in the tgHD rat and affective disturbances in HD patients.
authors.affiliation: Department of Neuroanatomy and Molecular Brain Research, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petrasch-Parwez
authors.forename: Huu-Phuc
authors.initials: HP
authors.lastname: Nguyen
authors.forename: Marlen
authors.initials: M
authors.lastname: Löbbecke-Schumacher
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Habbes
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieczorek
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Karl-Hermann
authors.initials: KH
authors.lastname: Andres
authors.forename: Rolf
authors.initials: R
authors.lastname: Dermietzel
authors.forename: Stephan
authors.initials: S
authors.lastname: Von Hörsten
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins