Antipsychotic drugs cause glial cell line-derived neurotrophic factor secretion from C6 glioma cells.
OBJECTIVE
Atypical antipsychotic drugs have been shown to protect PC12 cells from cell death induced by a variety of stimuli in culture. Recently, it has been postulated that trophic factors, such as brain-derived neurotrophic factor (BDNF), play a role in preventing cell death. It has been shown that antipsychotic drugs attenuate the decrease in rat hippocampal BDNF that results from immobilization-induced stress. We aimed to determine whether the neuroprotective effects of antipsychotic drugs could be mediated through glial cell line-derived neurotrophic factor (GDNF).


METHODS
We investigated the effects of the atypical antipsychotic drugs quetiapine and clozapine and the typical antipsychotic haloperidol on the secretion of GDNF from rat C6 glioma cells.


RESULTS
All 3 drugs increased the amount of GDNF secreted from C6 glioma cells into the medium after 48-hour culture. The intracellular content of GDNF was not altered by treatment with any of the antipsychotic drugs. None of the antipsychotic drugs decreased cell number.


CONCLUSIONS
This study suggests that stimulation of GDNF release from glial cells by antipsychotic drugs might underlie some of their neuroprotective properties in situ.
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon.
Zongjun
Z
Shao
Lillian E
LE
Dyck
Haitao
H
Wang
Xin-Min
XM
Li
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003024:Clozapine / Q000494:pharmacology; D003987:Dibenzothiazepines / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D000069348:Quetiapine Fumarate; D051381:Rats
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D000069348:Quetiapine Fumarate; D003024:Clozapine; D006220:Haloperidol