Glia as a putative target for antidepressant treatments.
BACKGROUND
Since the early 1950s, various molecular mechanisms have been invoked to explain how antidepressants work. The most recent suggests that pharmacologically stimulated adult neurogenesis might be involved. Surprisingly, in the adult brain, an important source of new neurons and possibly mediators of neurogenesis appears to be glia, i.e., astrocytes. We have recently shown that protracted administration of the antidepressant fluoxetine to adult rats upregulated the astrocytic protein S100beta content and increased neurogenesis in the hippocampus.


METHODS
Rats were treated with fluoxetine for 21 days; before sacrifice bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Immunofluorescence was used to identify proliferating BrdU-positive cells, and cells immunopositive for S100beta and its receptor receptor for advanced glycation end products (RAGE).


RESULTS
Typically, S100beta-positive cells were observed in the vicinity of BrdU-positive cells. On the other hand, we observed colocalization of RAGE receptors and BrdU immunoreactivities, suggesting that some proliferating cells express these receptors for S100beta. RAGE expression by neuronal cells or neuronal precursors and its activation by S100beta may promote their survival.


CONCLUSIONS
The anatomical localization of hippocampal S100beta, its receptor RAGE, and BrdU-positive cells that we describe in this study is only indicative of a putative role for glia in antidepressant-stimulated neurogenesis. Functional in vitro and in vivo studies are needed to directly investigate this role; quantitative assays and time-course studies are also warranted.


CONCLUSIONS
We propose that a better understanding of glia functioning could establish its role as a target for novel antidepressant treatments.
Manev
Hari
H
The Psychiatric Institute, Department of Psychiatry, University of Illinois, Chicago 1601 West Taylor Street, MC912, Chicago, IL 60612, USA. hmanev@psych.uic.edu
Uz
Tolga
T
Manev
Radmila
R
D000818:Animals; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005455:Fluorescent Antibody Technique; D005473:Fluoxetine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D005473:Fluoxetine; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D017367:Selective Serotonin Reuptake Inhibitors