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Serotoninergic control of the activity and expression of glial GABA transporters in the rat cerebellum
Author(s) -
Voutsinos Brigitte,
Dutuit Magali,
Reboul Ariel,
FevreMontange Michelle,
Bernard Arlette,
Trouillas Paul,
Akaoka Hideo,
Belin MarieFrançoise,
DidierBazès Marianne
Publication year - 1998
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199805)23:1<45::aid-glia5>3.0.co;2-3
Subject(s) - biology , cerebellum , serotonergic , neuroscience , gaba transporter , central nervous system , serotonin , neurotransmitter , biochemistry , receptor
γ‐Aminobutyric acid (GABA) transporters (GAT‐1, GAT‐2, and GAT‐3) play a key role in the termination of GABA transmission and the regulation of extracellular GABA concentrations. In the present study, pharmacological, cellular, and molecular analyses provide evidence for a modulatory effect of serotoninergic neurons on the activity and expression of glial GABA transporters in the rat cerebellum. Degeneration of serotoninergic neurons after in vivo 5,7‐dihydroxytryptamine (5,7‐DHT) treatment resulted in a significant decrease (−27%) in [ 3 H]‐GABA uptake into cerebellar punches. This decrease probably occurred via inhibition of GAT‐2 or GAT‐3 activity since their inhibitor, β‐alanine, induced a decrease in [ 3 H]‐GABA uptake in punches of sham‐operated rats (−28%), but not in punches of 5,7‐DHT‐treated rats, demonstrating that serotonin terminal degeneration had already impaired the β‐alanine‐sensitive component of GABA uptake. In contrast, nipecotic acid, a preferential inhibitor of GAT‐1, induced comparable decreases in [ 3 H]‐GABA uptake comparable in punches of 5,7‐DHT (−38%) versus sham‐operated rats (−37%). The decreases in GAT‐1 (−16%), GAT‐2 (−34%), and GAT‐3 (−32%) mRNA levels after 5,7‐DHT treatment (detected by quantitative RT‐PCR) are consistent with a serotoninergic control of GABA transporter expression at the transcriptional level. The cellular distribution of GAT‐2 and GAT‐3 mRNA, shown by in situ hybridization, suggests a glial localization of these transporters in the cerebellum and demonstrated a preferential anatomical localization of GAT‐2 mRNA in the granular layer and of GAT‐3 mRNA in the deep cerebellar nuclei. A direct serotoninergic control of glial GABA uptake was further demonstrated in vitro since serotonin stimulated the activity and mRNA expression of the GABA transporters in cerebellar astrocyte cultures. GLIA 23:45–60, 1998. © 1998 Wiley‐Liss, Inc.