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Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia
Author(s) -
Stanwood Gregg D.,
Leitch Duncan B.,
Savchenko Valentina,
Wu Jane,
Fitsanakis Vanessa A.,
Anderson Douglas J.,
Stankowski Jeannette N.,
Aschner Michael,
McLaughlin BethAnn
Publication year - 2009
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 - 10.1111/j.1471-4159.2009.06145.x
Subject(s) - substantia nigra , pars compacta , dopaminergic , dopamine , medium spiny neuron , biology , striatum , manganese , tyrosine hydroxylase , basal ganglia , chemistry , medicine , endocrinology , central nervous system , organic chemistry
Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson’s disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alterations induced by manganese exposure. Primary mesencephalic cultures were treated with 10–800 μM manganese chloride which resulted in dramatic changes in the neuronal cytoskeleton even at subtoxic concentrations. Using cultures from mice with red fluorescent protein driven by the tyrosine hydroxylase (TH) promoter, we found that dopaminergic neurons were more susceptible to manganese toxicity. To understand the vulnerability of dopaminergic cells to chronic manganese exposure, mice were given i.p. injections of MnCl 2 for 30 days. We observed a 20% reduction in TH‐positive neurons in the substantia nigra pars compacta (SNpc) following manganese treatment. Quantification of Nissl bodies revealed a widespread reduction in SNpc cell numbers. Other areas of the basal ganglia were also altered by manganese as evidenced by the loss of glutamic acid decarboxylase 67 in the striatum. These studies suggest that acute manganese exposure induces cytoskeletal dysfunction prior to degeneration and that chronic manganese exposure results in neurochemical dysfunction with overlapping features to PD.