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.