title: In vitro S100B secretion is reduced by apomorphine: effects of antipsychotics and antioxidants.
abstract: Astrocytes express dopamine receptors and respond to dopamine stimulation. However, the role of astrocytes in psychiatric disorders and the effects of antipsychotics on astroglial cells have only been investigated recently. S100B is a glial-derived protein, commonly used as a marker of astroglial activation in psychiatric disorders, particularly schizophrenia. We investigated S100B secretion in three different rat brain preparations (fresh hippocampal slices, C6 glioma cells and primary astrocyte cultures) exposed to apomorphine and antipsychotics (haloperidol and risperidone), aiming to evaluate, ex vivo and in vitro, whether dopamine activation and dopaminergic antagonists modulate astroglial activation, as measured by changes in the extracellular levels of S100B. The serum S100B elevation observed in schizophrenic patients is not reflected by the in vitro decrease of S100B secretion that we observed in hippocampal slices, cortical astrocytes and C6 glioma cells treated with apomorphine, which mimics dopaminergic hyperactivation. This decrease in S100B secretion can be explained by a stimulation of D2 receptors negatively coupled to adenyl cyclase. Antipsychotic medications and antioxidant supplementation were able to prevent the decline in S100B secretion. Findings reinforce the benefits of antioxidant therapy in psychiatric disorders. Based on our results, in hippocampal slices exposed to apomorphine, it may be suggested that antipsychotics could help to normalize S100B secretion by astrocytes.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. patricianardin@yahoo.com.br
authors.forename: Patrícia
authors.initials: P
authors.lastname: Nardin
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Tramontina
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.forename: Lucas S
authors.initials: LS
authors.lastname: Tortorelli
authors.forename: Paula
authors.initials: P
authors.lastname: Lunardi
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Klein
authors.forename: Krista M
authors.initials: KM
authors.lastname: Wartchow
authors.forename: Larissa D
authors.initials: LD
authors.lastname: Bobermin
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
authors.forename: Elaine
authors.initials: E
authors.lastname: Elisabetsky
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology*; D001058:Apomorphine / Q000378:metabolism / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005910:Glioma / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D007770:L-Lactate Dehydrogenase; D001058:Apomorphine