Premium
Dopamine‐dependent neurotoxicity of lipopolysaccharide in substantia nigra
Author(s) -
De Pablos Rocío M.,
Herrera Antonio J.,
Villarán Ruth F.,
Cano Josefina,
Machado Alberto
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2153fje
Subject(s) - substantia nigra , tyrosine hydroxylase , dopaminergic , dopamine , neurotoxicity , lipopolysaccharide , chemistry , pharmacology , population , microglia , endocrinology , inflammation , medicine , toxicity , environmental health
Intranigral injection of lipopolysaccharide (LPS), a potent inductor of inflammation, induces degeneration of dopaminergic neurons, along with an inflammatory process that features activation of microglial cells and loss of astrocytes. To test the involvement of dopamine (DA) in this degeneration induced by LPS, we treated albino Wistar rats with different concentrations of α‐methyl‐ p ‐tyrosine (α‐MPT), an inhibitor of tyrosine hydroxylase (TH) activity. Results showed that α‐MPT prevented LPS‐induced loss of TH immunostaining and expression of mRNA for TH and DA transporter; it also prevented substantial activation of microglial cells. Loss of the astroglial population, a marker of damage in our model, was also prevented. This protective effect resulted from inhibition of TH and the consequent decrease in DA concentration, because treatment with l ‐DOPA/benserazide, which bypasses TH inhibition induced by α‐MPT, reversed the protective effect produced by this drug. These results point out the important contribution of DA to the vulnerability and degeneration of dopaminergic neurons of the substantia nigra. Knowledge about the involvement of DA in this process may lead to the possibility of new protection strategies against this important degenerative process.