Serotonin innervation of Lurcher mutant mice: basic data and manipulation with a combination of amantadine, thiamine and L-tryptophan.
The Lurcher (Lc/+) mutant mouse is characterized by a considerable atrophy of the cerebellum due to a massive loss of cerebellar Purkinje and granule cells, as well as of neurons from the inferior olivary nucleus. In this study the effects of a therapeutic combination of amantadine, thiamine and L-tryptophan on the serotonin (5-HT) innervation was assessed in Lurcher mice by autoradiography, using [3H]citalopram to label 5-HT transporters. In wild type mice as well as in both saline-treated and drug-treated Lurcher mutants, [3H]citalopram binding remained unchanged in forebrain and brainstem regions. In the cerebellum, labelling of deep cerebellar nuclei (CBnuc) was about twofold higher than in the cortex (CBctx). In saline-treated Lurcher mutants compared to wild type mice, the densities of [3H]citalopram were 98% higher in CBctx, and 180% higher in CBnuc. In CBctx of drug-treated Lurcher mutants, transporter densities were 89% higher than in the wild type, but did not differ from the saline-treated Lurcher. In the CBnuc of the drug-treated Lurcher mutants, [3H]citalopram binding was 50% higher than in the saline-treated Lurcher group, and 320% higher than in wild type mice. The results show that 5-HT transporters, already upregulated in the CBnuc of Lurcher mutant mice, can be further increased by a pharmacological treatment, possibly altering the availability of 5-HT in some of its target areas.
Le Marec
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Centre for Research in Neurological Sciences, Department of Physiology, Faculty of Medicine, University of Montréal, CHUM--Hôtel-Dieu Hospital, Québec, Canada.
Hébert
C
C
Botez
M I
MI
Botez-Marquard
T
T
Marchand
L
L
Reader
T A
TA
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D001933:Brain Stem / Q000033:anatomy & histology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D015283:Citalopram; D005260:Female; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins; D016548:Prosencephalon / Q000033:anatomy & histology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D013831:Thiamine / Q000494:pharmacology*; D014364:Tryptophan / Q000494:pharmacology*
D006916:5-Hydroxytryptophan; D000547:Amantadine; D000978:Antiparkinson Agents; D002352:Carrier Proteins; D015283:Citalopram; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D013831:Thiamine; D014364:Tryptophan; C493231:Slc6a4 protein, mouse