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Thrombin induces in vivo degeneration of nigral dopaminergic neurones along with the activation of microglia
Author(s) -
CarreñoMüller Eloisa,
Herrera Antonio J.,
De Pablos Rocio M.,
TomásCamardiel Mayka,
Venero José L.,
Cano Josefina,
Machado Alberto
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01634.x
Subject(s) - tyrosine hydroxylase , thrombin , substantia nigra , dopaminergic , nigrostriatal pathway , immunostaining , chemistry , microglia , endocrinology , medicine , proinflammatory cytokine , dopamine , biology , inflammation , platelet , immunohistochemistry
Seven days after the injection of different concentrations of thrombin into the nigrostriatal pathway, a strong macrophage/microglial reaction was observed in the substantia nigra (SN), indicated by immunostaining, using OX‐42 and OX‐6 antibodies, and by the induction of iNOS, IL‐1α, Il‐1β and TNF‐α. Moreover, selective damage to dopaminergic neurones was produced after thrombin injection, evidenced by loss of tyrosine hydroxylase immunostaining and tyrosine hydroxylase mRNA‐expressing cell bodies, and the unaltered transcription of glutamic acid decarboxylase mRNA in the SN and striatum. These thrombin effects could be produced by its ability to induce the activation of microglia described in in vitro studies, and are in agreement with the effects described for other proinflammatory compounds. Thrombin effects are produced by its biological activity since they almost disappeared when thrombin was heat‐inactivated or injected along with its inhibitor α‐NAPAP. Thrombin is a multi‐functional serine protease rapidly produced from prothrombin at the sites of tissue injury, and also upon breakdown of the blood–brain barrier, which strongly suggests it could easily enter into the CNS. These results could have special importance in some degenerative processes of the nigrostriatal dopaminergic system.