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Behavioral, Neurochemical, and Electrophysiological Changes in an Early Spontaneous Mouse Model of Nigrostriatal Degeneration

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Abstract

In idiopathic Parkinson’s disease, clinical symptoms do not emerge until consistent neurodegeneration has occurred. The late appearance of symptoms implies the existence of a relatively long preclinical period during which several disease-induced neurochemical changes take place to mask the existence of the disease and delay its clinical manifestations. The aim of this study was to examine the neurochemical, neurophysiological, and behavioral changes induced by the loss of nigrostriatal innervation in the En1+/−;En2−/− mouse, in the 10 months following degeneration, compared to En2 null mutant mice. Behavioral analysis (Pole-test, Beam-walking test, and Inverted grid test) and field potential recordings in the striatum indicated that loss of ~70% of nigrostriatal neurons produced no significant functional effects until 8 months of age, when En1+/−;En2−/− animals started to show frank motor deficits and electrophysiological alterations in corticostriatal plasticity. Similarly, alterations in dopamine homeostasis, dopamine turnover, and dopamine innervation were observed in aged animals compared to young En1+/−;En2−/− mice. These data suggests that in En1+/−;En2−/− mice nigrostriatal degeneration in the substantia nigra is functionally compensated.

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Acknowledgments

We thank Martyn Goulding (Salk Institute, La Jolla, CA) and Alex Joyner (Memorial Sloan-Kettering Cancer Center, New York, NY) for initially providing the En1-tauLacZ and the En2 mutant mice. We thank Yuri Bozzi for helpful comments on the manuscript and Tommaso Schiavinotto for help with the statistical analysis. The authors would like also to thank Mrs Ornella Baroni for her precious help in animal care. This work was supported by PRIN grants “prot nr. 2005055445, anno 2005”.

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Authors and Affiliations

  1. Department of Neuroscience, Section of Pharmacology, University of Pisa, Pisa, Italy

    Paola Sgadò, Cristina Viaggi, Francesca Vaglini & Giovanni Umberto Corsini

  2. CNR Institute of Neuroscience, Cagliari, Italy

    Annalisa Pinna & Micaela Morelli

  3. Department of Toxicology, University of Cagliari, Cagliari, Italy

    Annalisa Pinna, Silvia Pontis & Micaela Morelli

  4. Experimental Neurology Laboratory, C.E.R.C., Fondazione Santa Lucia IRCCS, Rome, Italy

    Cristina Marrone & Nicola Biagio Mercuri

  5. Laboratory of Molecular Neuropathology, CNR Institute of Neuroscience, Centre for Integrative Biology (CIBIO), University of Trento, Via delle Regole 101, 38060, Mattarello, Trento (TN), Italy

    Paola Sgadò

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  1. Paola Sgadò
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  2. Cristina Viaggi
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  3. Annalisa Pinna
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  9. Giovanni Umberto Corsini
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Correspondence to Paola Sgadò.

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Sgadò, P., Viaggi, C., Pinna, A. et al. Behavioral, Neurochemical, and Electrophysiological Changes in an Early Spontaneous Mouse Model of Nigrostriatal Degeneration. Neurotox Res 20, 170–181 (2011). https://doi.org/10.1007/s12640-010-9232-9

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  • DOI: https://doi.org/10.1007/s12640-010-9232-9

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