PMID- 18219447
OWN - NLM
STAT- MEDLINE
DCOM- 20080620
LR  - 20221207
IS  - 0895-8696 (Print)
IS  - 0895-8696 (Linking)
VI  - 34
IP  - 3
DP  - 2008 Mar
TI  - Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in 
      rat c6 glioma cells through production of 5alpha-reduced neurosteroids.
PG  - 193-200
LID - 10.1007/s12031-007-9034-6 [doi]
AB  - Tricyclic antidepressants and selective serotonin reuptake inhibitors are 
      considered in theory to induce the outflow of neurotransmitters, norepinephrine, 
      and serotonin from the synapses as a consequence of inhibiting their reuptake 
      into the nerve terminals, resulting in the stimulation of glial cells surrounding 
      the synapses in the brain. Then, we have investigated the direct actions of 
      neurotransmitters on glial cell metabolism and function using rat C6 glioma cells 
      as an in vitro model system and suggested that these neurotransmitters induce 
      their differentiation probably through the production of 5alpha-reduced 
      neurosteroids. On the other hand, the stimulation of the glioma cells with 
      serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) 
      gene expression, which may be closely related to the beneficial effects of 
      antidepressant drugs. In the present study, to evaluate BDNF expression in 
      differentiated glial cells, the glioma cells were pretreated with progesterone, 
      and the effect of serotonin on BDNF messenger RNA levels in these cells was 
      examined. Progesterone pretreatment enhanced the stimulatory action of serotonin 
      on BDNF gene expression, and the enhancement of serotonin action observed in the 
      cells pretreated with progesterone was almost completely abolished by 
      finasteride, an inhibitor of the enzyme involved in the production of 
      5alpha-reduced neurosteroids. These findings propose the possibility that 
      neurosteroid-mediated glial cell differentiation may result in the enhancement of 
      serotonin-stimulated BDNF gene expression, which is considered to contribute to 
      the survival, regeneration, and plasticity of neuronal cells in the brain, and 
      hence, leading to the improvement of mood disorders and other symptoms in 
      depressive patients.
FAU - Morita, Kyoji
AU  - Morita K
AD  - Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 
      Kuramoto, Tokushima, 770-8503, Japan. km@basic.med.tokushima-u.ac.jp
FAU - Her, Song
AU  - Her S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080125
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 333DO1RDJY (Serotonin)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 57GNO57U7G (Finasteride)
RN  - EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase)
SB  - IM
MH  - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/drug effects/metabolism
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/pharmacology
MH  - Brain/*drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cell Differentiation/drug effects/genetics
MH  - Cell Line, Tumor
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Finasteride/pharmacology
MH  - Gene Expression Regulation/*drug effects/genetics
MH  - Glioma
MH  - Neuroglia/*drug effects/metabolism
MH  - Neuronal Plasticity/drug effects/genetics
MH  - Presynaptic Terminals/drug effects/metabolism
MH  - Progesterone/*pharmacology
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Serotonin/*pharmacology
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
MH  - Up-Regulation/drug effects/genetics
EDAT- 2008/01/26 09:00
MHDA- 2008/06/21 09:00
CRDT- 2008/01/26 09:00
PHST- 2007/08/09 00:00 [received]
PHST- 2007/12/13 00:00 [accepted]
PHST- 2008/01/26 09:00 [pubmed]
PHST- 2008/06/21 09:00 [medline]
PHST- 2008/01/26 09:00 [entrez]
AID - 10.1007/s12031-007-9034-6 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2008 Mar;34(3):193-200. doi: 10.1007/s12031-007-9034-6. Epub 2008 
      Jan 25.