title: Glutamate transporters: a key piece in the glutamate puzzle of major depressive disorder.
abstract: Glutamatergic therapies are emerging as the new path for the treatment of Major Depression Disorder. Recent reports reviewing the use of glutamate activity modulators in the treatment of resistant depression advocate the importance of understanding the alterations of the diverse components of this complex system in mood disorders. In this postmortem study we used in situ hybridization and microarray analysis to evaluate the gene expression of the membrane transporters SLC1A2 and SLCA3 and the vesicular transporter SLCA17A7 in the hippocampus of Major Depressive Disorder (MDD) and Bipolar Disorder (BPD) subjects. Samples from 8 controls, 11 MDD and 6 BPD subjects were processed for in situ hybridization using cRNA probes for SLC1A2, SLC1A3 and SLC17A7. Laser capture microdissection was used to collect tissue from adjacent sections for microarray analysis. The results showed that the expression of the membrane transporters SLC1A2 and SLC1A3 was diminished in the MDD group compared to controls. The expression of the vesicular glutamate transporter SLC17A7 on the other hand was increased in MDD subjects. As for the BPD group, all three transporters showed trends similar to those observed in MDD, but the changes observed did not reach significance. We hypothesize that the decreased expression of the membrane glutamate transporters and the increased expression of the vesicular transporter in the hippocampus would affect the balance of the glutamatergic circuitry of the hippocampus, and that this effect may be a major contributor to depressive symptoms.
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, United States. ammedina@umich.edu
authors.forename: Adriana
authors.initials: A
authors.lastname: Medina
authors.forename: Sharon
authors.initials: S
authors.lastname: Burke
authors.forename: Robert C
authors.initials: RC
authors.lastname: Thompson
authors.forename: William
authors.initials: W
authors.lastname: Bunney
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: Alan
authors.initials: A
authors.lastname: Schatzberg
authors.forename: Huda
authors.initials: H
authors.lastname: Akil
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
mesh_terms: D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000473:pathology; D003865:Major Depressive Disorder / Q000473:pathology*; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011180:Postmortem Changes; D012333:RNA, Messenger; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493464:SLC17A7 protein, human; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; D050598:Vesicular Glutamate Transport Protein 1
keywords: Bipolar disorder; Glutamate; Glutamate transporters; Hippocampus; In situ hybridization; Laser capture microdissection; Major depression disorder; Microarray