title: Timecourse of striatal re-innervation following lesions of dopaminergic SNpc neurons of the rat.
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.
authors.affiliation: Department of Medicine, Monash University, Monash Medical Centre, Clayton, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Stanic
authors.forename: D I
authors.initials: DI
authors.lastname: Finkelstein
authors.forename: D W
authors.initials: DW
authors.lastname: Bourke
authors.forename: J
authors.initials: J
authors.lastname: Drago
authors.forename: M K
authors.initials: MK
authors.lastname: Horne
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal; D001710:Biotin / Q000493:pharmacokinetics; D002452:Cell Count; D003911:Dextrans / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D013565:Sympatholytics / Q000633:toxicity*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D003911:Dextrans; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D013565:Sympatholytics; D001710:Biotin; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine