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

Cristina Baiguera1, Manuela Alghisi, Annalisa Pinna

  • 1Department of Biomedical Sciences and Biotechnologies, University of Brescia and National Institute of Neuroscience, 25123 Brescia, Italy.

Brain : a Journal of Neurology
|August 24, 2012
PubMed

Insights

Mice lacking the nuclear factor c-Rel develop Parkinson's disease-like symptoms with age, including neuron loss and motor deficits. These findings highlight c-Rel's role in protecting brain cells and suggest a new Parkinson's disease model.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Nuclear factor κB/c-Rel activation enhances neuronal resilience by regulating pro-survival genes.
  • Dysregulation of neuroprotective pathways is implicated in neurodegenerative diseases.

Purpose of the Study:

  • To investigate the role of c-Rel in neuronal resilience and its potential involvement in Parkinson's disease pathogenesis.
  • To characterize the neuropathology and behavioral deficits in c-Rel-deficient mice.

Main Methods:

  • Utilized c-Rel-deficient (c-rel(-/-)) mice aged to 18 months.
  • Assessed dopaminergic neuron loss via tyrosine hydroxylase-immunoreactivity and Nissl staining.
  • Quantified striatal dopamine and homovanillic acid levels.
  • Examined α-synuclein, DMT1, and iron expression.
  • Evaluated microglial and astrocytic reactivity.
  • Performed locomotor and gait analyses, followed by l-3,4-dihydroxyphenylalanine treatment.

Main Results:

  • Aged c-rel(-/-) mice exhibited significant loss of dopaminergic neurons in the substantia nigra pars compacta.
  • Nigral degeneration correlated with reduced striatal dopamine levels and dopaminergic terminals.
  • Increased α-synuclein, DMT1, and iron staining were observed in c-rel(-/-) mice.
  • These mice displayed age-dependent motor deficits, including bradykinesia and rigidity, which improved with L-DOPA treatment.

Conclusions:

  • c-Rel deficiency leads to Parkinson's disease-like neuropathology and motor impairments in aging mice.
  • c-Rel appears to be a critical regulator of substantia nigra pars compacta resilience.
  • Aged c-rel(-/-) mice represent a valuable model for studying Parkinson's disease.

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