Cyclosporin A attenuates the decrease in tyrosine hydroxylase immunoreactivity in nigrostriatal dopaminergic neurons and in striatal dopamine content in rats with intrastriatal injection of 6-hydroxydopamine

Kouji Matsuura, Hirofumi Makino, Norio Ogawa

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Abstract

To explore new therapeutic strategies for Parkinson's disease, we studied the possible protective effect of an immunosuppressant, cyclosporin A (CsA), treatment on changes in dopaminergic function in rats with intrastriatal injections of 6-hydroxydopamine (6-OHDA). Four weeks after injection of 6-OHDA, dopamine (DA) and dihydroxyphenylacetic acid in the striatum were depleted by 70-80%, and repeated high-dose CsA (20 mg/kg) treatment for 1 week significantly protected against these depletions. Tyrosine hydroxylase immunoreactivity (TH-IR) of the cell bodies in the substantia nigra pars compacta (SNc) ipsilateral to the injection were lower than on the contralateral side at 4 weeks but not at 1 week after 6-OHDA injection. The number of TH-positive cell bodies in the SNc decreased to 64% but CsA treatment increased this to 87%. The staining of microglia in the SN with OX42 and Griffonia simplicifolia B4 isolectin was intense at 3 days and gradually decreased by 28 days after injection. At 3 and 7 days after injection, the microglial staining in the SN was prominent and equal both in the 6-OHDA group and in ascorbic acid (SA)-injected controls. By 28 days postinjection, the staining had decreased to control levels in the SA group but was still above the control in the 6-OHDA group. CsA treatment did not affect this staining in either group. These results suggest that CsA protects against 6-OHDA-induced injury of nigrostriatal DA neurons by a mechanism not involving microglia.

Original languageEnglish
Pages (from-to)526-535
Number of pages10
JournalExperimental Neurology
Volume146
Issue number2
DOIs
Publication statusPublished - Jan 1 1997

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Corpus Striatum
Oxidopamine
Dopaminergic Neurons
Tyrosine 3-Monooxygenase
Cyclosporine
Dopamine
Injections
Staining and Labeling
Microglia
Therapeutics
Immunosuppressive Agents
Ascorbic Acid
Parkinson Disease
Acids
Wounds and Injuries

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

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title = "Cyclosporin A attenuates the decrease in tyrosine hydroxylase immunoreactivity in nigrostriatal dopaminergic neurons and in striatal dopamine content in rats with intrastriatal injection of 6-hydroxydopamine",
abstract = "To explore new therapeutic strategies for Parkinson's disease, we studied the possible protective effect of an immunosuppressant, cyclosporin A (CsA), treatment on changes in dopaminergic function in rats with intrastriatal injections of 6-hydroxydopamine (6-OHDA). Four weeks after injection of 6-OHDA, dopamine (DA) and dihydroxyphenylacetic acid in the striatum were depleted by 70-80{\%}, and repeated high-dose CsA (20 mg/kg) treatment for 1 week significantly protected against these depletions. Tyrosine hydroxylase immunoreactivity (TH-IR) of the cell bodies in the substantia nigra pars compacta (SNc) ipsilateral to the injection were lower than on the contralateral side at 4 weeks but not at 1 week after 6-OHDA injection. The number of TH-positive cell bodies in the SNc decreased to 64{\%} but CsA treatment increased this to 87{\%}. The staining of microglia in the SN with OX42 and Griffonia simplicifolia B4 isolectin was intense at 3 days and gradually decreased by 28 days after injection. At 3 and 7 days after injection, the microglial staining in the SN was prominent and equal both in the 6-OHDA group and in ascorbic acid (SA)-injected controls. By 28 days postinjection, the staining had decreased to control levels in the SA group but was still above the control in the 6-OHDA group. CsA treatment did not affect this staining in either group. These results suggest that CsA protects against 6-OHDA-induced injury of nigrostriatal DA neurons by a mechanism not involving microglia.",
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AU - Ogawa, Norio

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