Lower phosphorylated glycogen synthase kinase-3B levels in platelets of patients with schizophrenia: increment by olanzapine treatment.
Glycogen synthase kinase-3B (GSK-3B) is involved with important neuronal processes such as cell survival, gene regulation, mood and cognitive performance. This enzyme is inactivated by phosphorylation at the phospho-Ser9 site. We compared GSK-3B levels in patients with schizophrenia to a health control group. The levels of phosphorylated and total GSK-3B in platelets of ten drug-free patients, ten long-term olanzapine treated patients and 20 healthy controls were determined by means of an enzyme immunoassay kit. In drug-free patients, GSK-3B levels were accessed again after 8 weeks on treatment with olanzapine. At baseline, drug-free patients presented lower phosphorylated and total GSK-3B levels than healthy controls (p < 0.05). After 8 weeks on olanzapine treatment, phosphorylated and total GSK-3B levels were significantly increased (p < 0.01). Reduced phospho-Ser9-GSK-3B in schizophrenia may disrupt signal-transduction pathways and influence crucial cellular processes, such as transcription, apoptosis, stress response and cell proliferation. Further studies should clarify whether the increment of GSK-3B phosphorylation by olanzapine is related to its antipsychotic effects.
Laboratory of Neuroscience (LIM 27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr Ovídio Pires de Campos, 785, 3rd Floor, São Paulo, 05403-010, Brazil.
Aline Siqueira
AS
Ferreira
Nádia Rezende Barbosa
NR
Raposo
Paulo Clemente
PC
Sallet
Martinus Theodorus
MT
Van de Bilt
Rodrigo
R
Machado-Vieira
Leda Leme
LL
Talib
Wagner Farid
WF
Gattaz
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010766:Phosphorylation / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D013997:Time Factors
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D038362:Glycogen Synthase Kinase 3; D000077152:Olanzapine