Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients.
Reelin, a secretory protease that plays major roles in neurodevelopment and synaptic plasticity, may also play a role in the pathogenesis of schizophrenia. The present study was undertaken to examine whether the expression of two receptors for reelin, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (ApoER2), were abnormal in peripheral blood lymphocytes of schizophrenic patients. In this study, we measured the mRNA levels of VLDLR and ApoER2 in blood lymphocytes from patients with schizophrenia (drug-naive patients (n=20) and medicated patients (n=20)) and age-and gender-matched healthy controls (n=40) using quantitative real-time RT-PCR. Furthermore, we examined the correlation between mRNA levels and clinical variables in patients. Levels of VLDLR mRNA in drug-naive, unmedicated patients with schizophrenia were significantly lower than those of controls. In contrast, levels of ApoER2 mRNA in drug-naive patients did not differ from those of controls, although the levels of ApoER2 mRNA in medicated patients were significantly lower than those of controls. Interestingly, levels of VLDLR mRNA in drug-naive patients showed significant increases with respect to baseline after six months of antipsychotic treatment, whereas levels of ApoER2 mRNA were significantly lower than baseline after six months of treatment. In all patients, there was a negative correlation between VLDLR mRNA levels and the severity of clinical symptoms. Our findings suggest that peripheral VLDLR mRNA levels may serve as a reliable peripheral biological marker of schizophrenia, and that the reelin-VLDLR/ApoER2 signaling pathway plays a role in the pathophysiology of schizophrenia.
Suzuki
Katsuaki
K
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Nakamura
Kazuhiko
K
Iwata
Yasuhide
Y
Sekine
Yoshimoto
Y
Kawai
Masayoshi
M
Sugihara
Genichi
G
Tsuchiya
Kenji J
KJ
Suda
Shiro
S
Matsuzaki
Hideo
H
Takei
Nori
N
Hashimoto
Kenji
K
Mori
Norio
N
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D010054:Brief Psychiatric Rating Scale; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000235:genetics* / Q000378:metabolism; D000091042:Reelin Protein; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D012737:Sex Factors
D014150:Antipsychotic Agents; D015415:Biomarkers; D026502:LDL-Receptor Related Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C469363:reelin receptor; C000717127:RELN protein, human