title: Evidence for alterations of the glial syncytial function in major depressive disorder.
abstract: BACKGROUND
  Glial cells are essential in maintaining synaptic function. In glutamatergic synapses astrocytes remove the products of neural activity, (i.e. potassium, glutamate and excess water) from the synaptic cleft and redistribute them across the glial network; these products of neural activity can then be recycled for neuronal use or released into the vascular compartment. This type of highly coupled cell network -or syncytium-maintains the balance of synaptic activity by restoring the basal levels of such molecules in the synaptic cleft. Previous studies have reported alterations of glia related genes in Major Depressive Disorder, including some genes related to syncytial function.
  
  
  METHODS
  We used RNA isolated from hippocampal tissues of 13 MDD subjects and 10 healthy controls to broadly examine gene expression using microarrays. Hippocampal RNA samples were isolated by laser capture microdissection from human tissue sections carefully avoiding contamination from neighboring structures. Once RNA quality was validated RNA was labeled and hybridized to microarrays.
  
  
  RESULTS
  Analysis of microarray data identified mRNA transcripts involved in glial syncytial function that were downregulated in MDD subjects compared to controls, including potassium and water channels (KCNJ10, AQP4), gap junction proteins (GJA1) and glutamate transporters (SLC1A2, SLC1A3). These gene expression differences were confirmed by qPCR.
  
  
  CONCLUSIONS
  The downregulation of these genes related to the syncytial network activity of glial cells is consistent with the hypothesis that synaptic homeostasis is disrupted thereby disrupting hippocampal synaptic function in MDD patients. Such glial gene expression changes could contribute either to the onset or perpetuation of depressive symptoms and hence, represent targets for novel therapeutics.
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA. Electronic address: ammedina@umich.edu.
authors.forename: Adriana
authors.initials: A
authors.lastname: Medina
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
authors.affiliation: Department of Psychiatry, University of California, Irvine, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Bunney
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville AL, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.affiliation: Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Schatzberg
authors.affiliation: Psychiatry, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Barchas
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Huda
authors.initials: H
authors.lastname: Akil
authors.affiliation: Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D018031:Connexin 43 / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2; D015870:Gene Expression; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult; D000098854:Kcnj10 Channel
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D018031:Connexin 43; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C500216:GJA1 protein, human; D050491:Glutamate Plasma Membrane Transport Proteins; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human
keywords: Astrocytes; Depression; Glia; Glutamatergic synapse; Major depressive disorder