In vitro exposure of cultured porcine choroid plexus epithelial cells to immunosuppressant, anti-inflammatory, and psychoactive drugs.
Delivery of neurotrophic molecules to the CNS is a potential treatment for preventing the neuronal loss in neurological disorders such as Huntington's disease (HD). Choroid plexus (CP) epithelial cell transplants secrete several neurotrophic factors and are neuroprotective in rat and monkey animal models of HD. HD patients receiving CP transplants would likely receive a course of immunosuppressant/anti-inflammatory treatment postsurgery and would remain on psychoactive medications to treat their motor, psychiatric, and emotional symptoms. Therefore, we examined whether CP epithelial cells are impacted by incubation with cyclosporine A (CsA), dexmethasone, haloperidol, fluoxetine, and carbamezapine. In each case, DNA was quantified to determine cell number, a formazen dye-based assay was used to quantify cell metabolism, and vascular endothelial growth factor (VEGF) levels were measured as a marker of protein secretion. Except for the highest dose of fluoxetine, none of the drugs tested exerted any detrimental effect on cell number. Incubation with CsA or dexamethasone did not have any consistent significant effect on VEGF secretion or cell metabolism. Carbamazepine was without effect while only the highest dose of haloperidol tested modestly lowered cell metabolism. VEGF secretion and cell metabolism was not measurable from CP cells exposed to 100 microM fluoxetine. These data continue to support the potential use of CP transplants in HD.
Emerich
Dwaine F
DF
LCT BioPharma, Inc., Providence, RI, USA. ED3FJM@aol.com
Schneider
Patricia
P
Bintz
Briannan
B
Hudak
Jebecka
J
Thanos
Christopher G
CG
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D034421:Sus scrofa; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D007166:Immunosuppressive Agents; D009281:Naphthalenes; D011619:Psychotropic Drugs; D042461:Vascular Endothelial Growth Factor A; D005473:Fluoxetine; C071003:nafenodone; D016572:Cyclosporine; D006220:Haloperidol