title: The glycolytic enzyme aldolase C is up-regulated in rat forebrain microsomes and in the cerebrospinal fluid after repetitive fluoxetine treatment.
abstract: The antidepressant drug fluoxetine is widely used for the treatment of a broad range of psychiatric disorders. Its mechanism of action is thought to involve cellular adaptations that are induced with a slow time course after initiation of treatment. To gain insight into the signaling pathways underlying such changes, the expression levels of proteins in a microsomal sub-fraction enriched in intracellular membranes from the rat forebrain was analyzed after two weeks of treatment with fluoxetine. Proteins were separated by two-dimensional gel electrophoresis, and the differentially regulated protein spots were identified by mass spectrometry. Protein network analysis suggested that most of the identified proteins could potentially be regulated by the insulin family of proteins. Among them, Fructose-bisphosphate aldolase C (AldoC), a glycolytic/gluconeogenic enzyme primarily expressed in forebrain astrocytes, was up-regulated 7.6-fold. An immunohistochemical analysis of the dorsal hippocampus revealed a robust decrease (43±2%) in the co-localization of AldoC and the astrocyte marker GFAP and a diffuse staining pattern, compatible with AldoC secretion into the extracellular space. Consistently, AldoC, contained in an exosome-like fraction in astrocyte conditioned medium, increased significantly in the cerebrospinal fluid. Our findings strongly favor a non-canonic signaling role for AldoC in cellular adaptations induced by repetitive fluoxetine treatment.
authors.affiliation: Laboratorio de Neurociencias, Universidad de Los Andes, Santiago, Chile.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Sandoval
authors.forename: Alejandro
authors.initials: A
authors.lastname: Luarte
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Herrera-Molina
authors.forename: Manuel
authors.initials: M
authors.lastname: Varas-Godoy
authors.forename: Marcos
authors.initials: M
authors.lastname: Santibáñez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rubio
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: Ka-Wan
authors.initials: KW
authors.lastname: Li
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Smalla
authors.forename: Ursula
authors.initials: U
authors.lastname: Wyneken
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005473:Fluoxetine / Q000494:pharmacology*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D007150:Immunohistochemistry; D008861:Microsomes / Q000201:enzymology; D016548:Prosencephalon / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D015854:Up-Regulation
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D005634:Fructose-Bisphosphate Aldolase