Late-onset Parkinsonism in NFκB/c-Rel-deficient mice

Cristina Baiguera, Manuela Alghisi, Annalisa Pinna, Arianna Bellucci, Maria Antonietta De Luca, Lucia Frau, Micaela Morelli, Rosaria Ingrassia, Marina Benarese, Vanessa Porrini, Michele Pellitteri, Giuseppe Bertini, Paolo Francesco Fabene, Sandra Sigala, Maria Grazia Spillantini, Hsiou Chi Liou, Pier Franco Spano, Marina Pizzi

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2750-2765
Number of pages16
JournalBrain
Volume135
Issue number9
DOIs
Publication statusPublished - 2012

Fingerprint

Parkinsonian Disorders
Gait
Parkinson Disease
Synucleins
Noxae
Staining and Labeling
Muscle Rigidity
Hypokinesia
Homovanillic Acid
Dihydroxyphenylalanine
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Substantia Nigra
Locomotion
Basal Ganglia
Superoxide Dismutase
Dopamine
Iron
Pars Compacta
Brain

Keywords

  • l-DOPA
  • motor impairments
  • NFκB/c-Rel
  • Parkinson's disease
  • α-synuclein

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Baiguera, C., Alghisi, M., Pinna, A., Bellucci, A., De Luca, M. A., Frau, L., ... Pizzi, M. (2012). Late-onset Parkinsonism in NFκB/c-Rel-deficient mice. Brain, 135(9), 2750-2765. https://doi.org/10.1093/brain/aws193

Late-onset Parkinsonism in NFκB/c-Rel-deficient mice. / Baiguera, Cristina; Alghisi, Manuela; Pinna, Annalisa; Bellucci, Arianna; De Luca, Maria Antonietta; Frau, Lucia; Morelli, Micaela; Ingrassia, Rosaria; Benarese, Marina; Porrini, Vanessa; Pellitteri, Michele; Bertini, Giuseppe; Fabene, Paolo Francesco; Sigala, Sandra; Spillantini, Maria Grazia; Liou, Hsiou Chi; Spano, Pier Franco; Pizzi, Marina.

In: Brain, Vol. 135, No. 9, 2012, p. 2750-2765.

Research output: Contribution to journalArticle

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 2012, 'Late-onset Parkinsonism in NFκB/c-Rel-deficient mice', Brain, vol. 135, no. 9, pp. 2750-2765. https://doi.org/10.1093/brain/aws193
Baiguera C, Alghisi M, Pinna A, Bellucci A, De Luca MA, Frau L et al. Late-onset Parkinsonism in NFκB/c-Rel-deficient mice. Brain. 2012;135(9):2750-2765. https://doi.org/10.1093/brain/aws193
Baiguera, Cristina ; Alghisi, Manuela ; Pinna, Annalisa ; Bellucci, Arianna ; De Luca, Maria Antonietta ; Frau, Lucia ; Morelli, Micaela ; Ingrassia, Rosaria ; Benarese, Marina ; Porrini, Vanessa ; Pellitteri, Michele ; Bertini, Giuseppe ; Fabene, Paolo Francesco ; Sigala, Sandra ; Spillantini, Maria Grazia ; Liou, Hsiou Chi ; Spano, Pier Franco ; Pizzi, Marina. / Late-onset Parkinsonism in NFκB/c-Rel-deficient mice. In: Brain. 2012 ; Vol. 135, No. 9. pp. 2750-2765.
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