Behavioural and biochemical characterization of c-Rel mutant mice as model of Parkinson’s diseas (Contributo in atti di convegno)

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  • Behavioural and biochemical characterization of c-Rel mutant mice as model of Parkinson’s diseas (Contributo in atti di convegno) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Alternative label
  • Pinna A, Pontis S, Pizzi M, Morelli M (2009)
    Behavioural and biochemical characterization of c-Rel mutant mice as model of Parkinson’s diseas
    in XVIII WFN World Congress on Parkinson's Disease and Related Disorders, Miami, 13-16 dicembre 2009
    (literal)
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  • Pinna A, Pontis S, Pizzi M, Morelli M (literal)
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  • S92 (literal)
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  • Abstracts of WFN XVIII World Congress on Parkinson's Disease and Related Disorders (literal)
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  • 15 (literal)
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  • 1 (literal)
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  • 2 (literal)
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  • 1CNR Institute of Neuroscience, 2Department of Toxicology, University of Cagliari, Cagliari, 3Department of Biochemical Sciences and Biotechnology, University of Brescia, Brescia, Italy (literal)
Titolo
  • Behavioural and biochemical characterization of c-Rel mutant mice as model of Parkinson’s diseas (literal)
Abstract
  • Background: Parkinson's Disease (PD) available animal models differ substantially from the human pathology with regard to onset of nigrostriatal neurons degeneration which occurs rapidly upon a toxic insult in animal models and in multi-factorial, slow and progressive manner in human. The over-activation of the nuclear transcription factor kappaB (NF-kB) has been observed in dying neurons of brains exposed to trauma and ischemia, as well as in brains of patients with PD and Alzheimer's disease. Experimental evidence demonstrated the presence of a progressive degeneration of nigrostriatal dopaminergic neurons in mice with a selective deletion of the c-Rel subunit of the NF-kB. Aims: We investigated whether mice lacking the c-Rel subunit (c-rel-/- mice) might represent a model of progressive PD, by using, a battery of behavioural tests evaluating spontaneous motor activity, strength of limb grasping, motor performance and coordination. Moreover, we assessed biochemical parameters such as alphasynuclein and hyperphosphorylated tau inclusions in different CNS areas. Results: c-rel-/- mice displayed deficits in strength of limb and, with aging, deficits of motor activity and motor coordination. Moreover, neuronal cell loss in the substantia nigra was associated with the appearance of neuropathological markers of neurodegeneration as accumulation of alpha-synuclein inclusions in nigral dopaminergic cells and hyperphosphorylated tau inclusions in hippocampal neurons. Conclusions: The spontaneous neurodegeneration occurring in c-rel-/- mice suggest that c-Rel may act as a regulator of neuronal vulnerability in the substantia nigra during aging and might be implicated in the pathogenesis of sporadic forms of parkinsonisms. (literal)
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