抄録
Recent lines of evidence suggest that affective disorders such as depression are based on synaptic dysfunction in the brain. Bilateral olfactory bulbectomy (OBX) is an experimental model for depression in rodents. Altered emotional state and increased locomotor activity gradually become remarkable after OBX. It has also been known that change in several neurotransmitter systems and alteration of neuronal networks in the limbic system after OBX. To identify the molecular nature of the synaptic alteration in the OBX brain, we analyzed by quantitative RT-PCR change in the expression level of several synaptic function-related genes, including synapsin I, NMDA receptor subunit 1 (NR1), drebrin A, PSD-95, BDNF and c-fos, in the hippocampus 2 and 4 weeks after OBX. As reported previously in rat, we observed transient increase in the level of BDNF mRNA 2 weeks after OBX. The levels of NR1 and synapsin I mRNAs were also slightly increased. The levels of these mRNAs went back to the baseline by next 2 weeks. In this time point we found the decrease in c-fos and drebrin A mRNAs. Furthermore, we observed that increase in nocturnal activity measured 4 weeks after OBX was greater in drebrin A-knockout mice (n = 6) than that in wild-type mice (n = 6). Loss of drebrin A may lead to a subsequent synaptic dysfunction in the hippocampus of OBX mice. Thus, our data suggest that drebrin A is a candidate vulnerability molecule in a certain type of affective disorders. [J Physiol Sci. 2008;58 Suppl:S56]
