3.4 Chronic D-serine treatment reverses the CSDS-induced increase BDNF signaling pathway in the NAc
To investigate the potential mechanisms underlying D-serine-induced antidepressant effects, we inspected the expression of BDNF signaling pathway proteins levels. Data are summarized in Figure 4A. The BDNF expression level was expressed as a ratio of the expression of β-Actin. As shown in Figure 4, CSDS increased NAc BDNF and pTrkB protein levels compared with the control, which was similar as reported(Dong et al., 2017). Compared with the CSDS group, D-serine treatment significantly decreased their expression. The CREB in the NAc is a significant mediator of neural plasticity and the transcription factor for BDNF. D-serine decreased pCREB level in the NAc of CSDS mice. Thus, D-serine treatment prevented the ability of stress to higher BDNF, pTrkB and pCREB in the NAc. In contrast, the total TrkB and CREB levels were unchanged among all the groups. Moreover, the D-serine-induced decrease in NAc BDNF expression of defeated mice was also improved by K252a treatment (n=5; Figure 4). In line with this, K252a also enhanced the effects of D-serine on the expression of NAc pTrkB, and pCREB (n=5; Figure 4). However, the level of total TrkB and CREB protein was not altered. Thus, D-serine-induced changes in the BDNF signaling pathway in the NAc are involved in the mediation of depression.