Timecourse of striatal re-innervation following lesions of dopaminergic SNpc neurons of the rat

Authors

  • D. Stanic,

    1. Department of Medicine, Monash University, Monash Medical Centre, Clayton, Australia
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    • *

      D.S. and D.I.F. contributed equally to this work and should be considered equal first authors.

  • D. I. Finkelstein,

    1. Department of Medicine, Monash University, Monash Medical Centre, Clayton, Australia
    2. Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria, 3010, Australia
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    • *

      D.S. and D.I.F. contributed equally to this work and should be considered equal first authors.

  • D. W. Bourke,

    1. Department of Medicine, Monash University, Monash Medical Centre, Clayton, Australia
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  • J. Drago,

    1. Department of Medicine, Monash University, Monash Medical Centre, Clayton, Australia
    2. Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria, 3010, Australia
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  • M. K. Horne

    1. Department of Medicine, Monash University, Monash Medical Centre, Clayton, Australia
    2. Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria, 3010, Australia
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: Professor M. Horne, at Howard Florey Institute, as above.
E-mail: m.horne@hfi.unimelb.edu.au

Abstract

Previously we described the extent of sprouting that axons of the rat substantia nigra pars compacta (SNpc) undergo to grow new synapses and re-innervate the dorsal striatum 16 weeks after partial lesions. Here we provide insights into the timing of events related to the re-innervation of the dorsal striatum by regenerating dopaminergic nigrostriatal axons over a 104-week period after partial SNpc lesioning. Density of dopamine transporter and tyrosine hydroxylase immunoreactive axonal varicosities (terminals) decreased up to 80% 4 weeks after lesioning but returned to normal by 16 weeks, unless SNpc lesions were greater than 75%. Neuronal tracer injections into the SNpc revealed a 119% increase in axon fibres (4 mm rostral to the SNpc) along the medial forebrain bundle 4 weeks after lesioning. SNpc cells underwent phenotypic changes. Four weeks after lesioning the proportion of SNpc neurons that expressed tyrosine hydroxylase fell from 90% to 38% but returned to 78% by 32 weeks. We discuss these phenotype changes in the context of neurogenesis. Significant reductions in dopamine levels in rats with medium (30–75%) lesions returned to normal by 16 weeks whereas recovery was not observed if lesions were larger than 75%. Finally, rotational behaviour of animals in response to amphetamine was examined. The clear rightward turning bias observed after 2 weeks recovered by 16 weeks in animals with medium (30–75%) lesions but was still present when lesions were larger. These studies provide insights into the processes that regulate sprouting responses in the central nervous system following injury.

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