2011 Volume 36 Pages 32-45
Leukemia inhibitory factor-receptor (LIFR) is known to play a major role in neurogenesis promotions and stem cell self-renewal via binding to their ligands, leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF). We hypothesized that LIFR may also play a role in the pathogenesis of schizophrenia. To test this, we performed clinical and animal studies. First, we measured the mRNA levels of LIFR, LIF and CNTF in peripheral lymphocytes from drug-naive patients with schizophrenia (n=22) and from age-and gender- matched healthy controls (n=44) using quantitative real-time RT-PCR. Levels of LIFR mRNA in patients with schizophrenia were significantly lower than those of controls. Expression of LIF mRNA was below the detectable level in both patients and controls. Levels of CNTF mRNA were similar between patients and controls. Second, we evaluated behavioral features in heterozygous LIFR knockout (LIFR^<+/->) mice, in which adult neurogenesis is known to be altered. Interestingly, LIFR^<+/-> mice showed dopaminergic hypersensitivity, which was shown by exacerbated methamphetamine-induced hyperlocomotion, compared to wildtype mice. These findings appear to support our hypothesis and suggest that LIFR may play a role in dopaminergic hypersensitivity.
