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Titolo: Late-onset Parkinsonism in NFκB/c-Rel-deficient mice
Autori: 
Data di pubblicazione: 2012
Rivista: 
BRAIN  
Citazione: Late-onset Parkinsonism in NFκB/c-Rel-deficient mice / Baiguera, C; Alghisi, M; Pinna, A; Bellucci, A; DE LUCA, Ma; Frau, L; Morelli, M; Ingrassia, R; Benarese, M; Porrini, V; Pellitteri, M; Bertini, G; Fabene, Pf; Sigala, S; Spillantini, Mg; Liou, Hc; Spano, Pf; Pizzi, M. - In: BRAIN. - ISSN 0006-8950. - 135:9(2012), pp. 2750-2765.
Abstract: Activation of the nuclear factor κB/c-Rel can increase neuronal resilience to pathological noxae by regulating the expression of pro-survival manganese superoxide dismutase (MnSOD, now known as SOD2) and Bcl-xL genes. We show here that c-Rel-deficient (c-rel(-/-)) mice developed a Parkinson's disease-like neuropathology with ageing. At 18 months of age, c-rel(-/-) mice exhibited a significant loss of dopaminergic neurons in the substantia nigra pars compacta, as assessed by tyrosine hydroxylase-immunoreactivity and Nissl staining. Nigral degeneration was accompanied by a significant loss of dopaminergic terminals and a significant reduction of dopamine and homovanillic acid levels in the striatum. Mice deficient of the c-Rel factor exhibited a marked immunoreactivity for fibrillary α-synuclein in the substantia nigra pars compacta as well as increased expression of divalent metal transporter 1 (DMT1) and iron staining in both the substantia nigra pars compacta and striatum. Aged c-rel(-/-) mouse brain were characterized by increased microglial reactivity in the basal ganglia, but no astrocytic reaction. In addition, c-rel(-/-) mice showed age-dependent deficits in locomotor and total activity and various gait-related deficits during a catwalk analysis that were reminiscent of bradykinesia and muscle rigidity. Both locomotor and gait-related deficits recovered in c-rel(-/-) mice treated with l-3,4-dihydroxyphenylalanine. These data suggest that c-Rel may act as a regulator of the substantia nigra pars compacta resilience to ageing and that aged c-rel(-/-) mice may be a suitable model of Parkinson's disease.
Handle: http://hdl.handle.net/11584/95385
Tipologia:1.1 Articolo in rivista

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