Abstract graphic.
The BDNF-TrkB signaling pathway and its downstream cascades are involved
in the synthesis of synapses which then regulates learning and memory.
Intraperitoneal injection of LPS damages the BDNF-TrkB signaling pathway
and its downstream cascade leading to cognitive dysfunction. 7,8-DHF can
penetrate the blood-brain barrier and activate TrkB receptors,
alleviating learning and memory deficits.
Figure 1. Behavioral tests and pro-inflammation levels in LPS
mice. (A-C) There was no significant difference in the time spent in
exploring the same objects between the Control and LPS mice during the
training phase. In the testing phase, when exposed to the novel object,
LPS mice spent less time on the novel object and presented lower
discrimination ratio compared with the Control group (n=10). (D)
Compared to the Control mice, the concentration of IL-1β, IL-6 and TNF-α
serum levels were significantly increased in LPS mice (n=4). Data are
presented as mean ± SEM. *P < 0.05; **P< 0.01; ****P < 0.0001.
Figure 2. The protein levels of the BDNF-TrkB signaling pathway
and its downstream cascades in the hippocampus. (A-D) Compared
with the Control mice, the levels of BDNF and p-TrkB proteins were
decreased in LPS mice, no difference was found in the expression of TrkB
(n=4). (E-G) The protein level of Bax was increased and the level of
Bcl-2 was reduced in the LPS group compared to the Control group (n=4).
(H-S) The protein expression of p-ERK1/2, p-CaMK2, p-CREB and p-GluR1 in
LPS mice was lower than in Control mice. There was no statistical
difference in the levels of ERK1/2, CaMK2, CREB and GluR1 proteins
between the Control and LPS groups (n=4). Data are presented as mean ±
SEM. *P < 0.05; **P < 0.01;
***P < 0.001.
Figure 3. The protein levels of the BDNF-TrkB signaling pathway
and its downstream cascades in the mPFC. (A-D) The protein levels of
BDNF and p-TrkB were reduced in LPS mice compared to the Control mice,
and no difference was found in the level of TrkB between these two
groups (n=4). (E-G) Compared with the Control group, the expression of
Bax was increased and the level of Bcl-2 was decreased in LPS group
(n=4). (H-S) The expression of p-ERK1/2, p-CaMK2, p-CREB and p-GluR1 in
LPS mice were downregulated. There was no statistical difference in the
levels of ERK1/2, CaMK2, CREB and GluR1 proteins between the Control and
LPS groups (n=4). Data are presented as mean ± SEM. *P< 0.05; **P < 0.01; ***P <
0.001; ****P < 0.0001.
Figure 4. The protein levels of the BDNF-TrkB signaling pathway
and its downstream cascades in the EC. (A-D) The expression of BDNF and
p-TrkB were decreased in LPS mice compared to Control mice, and no
statistical difference was observed in the expression of TrkB between
these two groups (n=4). (E-G) The level of Bax was up-regulated and the
level of Bcl-2 was decreased in the LPS group compared to Control mice
(n=4). (H-S) The expression of p-CaMK2 and p-CREB was decreased in LPS
mice. There was no significant difference in protein levels of ERK1/2,
p-ERK1/2, CaMK2, CREB, GluR1 and p-GluR1 between the Control and LPS
groups (n=4). Data are presented as
mean ± SEM. *P < 0.05; **P < 0.01.
Figure 5. 7,8-DHF alleviated LPS-induced learning and memory
deficits in the mice. (A-C) During the training phase, there was no
statistical difference in the time spent with objects after using
7,8-DHF or ANA12 in LPS mice. In the testing phase, the time spent on
the novel object and the discrimination ratio were increased in LPS mice
after administration of 7,8-DHF, however, ANA12 completely reversed the
effects of 7,8-DHF (n=10). Data are presented as mean ± SEM. ***P< 0.001; ****P < 0.0001; N.S. P> 0.05.
Figure 6. 7,8-DHF restored the LPS-induced BDNF-TrkB signaling
pathway and its downstream cascade disorders in the hippocampus. (A-D)
There were no statistical changes in the expression of BDNF and TrkB in
LPS mice after using 7,8-DHF or ANA12. The expression of p-TrkB was
increased in LPS mice after using 7,8-DHF, however, ANA12 reversed the
effects of 7,8-DHF (n=5). (E-G) 7,8-DHF decreased the expression of Bax
and increased the level of Bcl-2 in LPS mice, while ANA12 completely
reversed these changes (n=5). (H-S) The expression of p-ERK1/2, p-CaMK2,
p-CREB and p-GluR1 in LPS mice was increased after using 7,8-DHF,
however, ANA12 reversed the effects of 7,8-DHF. No statistical
differences were observed in protein levels of ERK1/2, CaMK2, CREB and
GluR1 in LPS groups after using 7,8-DHF or ANA12 (n=5). Data are
presented as mean ± SEM. *P < 0.05; **P< 0.01; ***P < 0.001; N.S. P> 0.05.
Figure 7. 7,8-DHF restored the LPS-induced BDNF-TrkB signaling
pathway and its downstream cascades disorder in the mPFC. (A-D) There
were no significant differences in protein levels of BDNF and TrkB in
LPS mice after administration of 7,8-DHF or ANA12. The level of p-TrkB
was increased in LPS mice after administration of 7,8-DHF, however,
ANA12 reversed the effects of 7,8-DHF (n=5). (E-G) The level of Bax was
reduced and the level of Bcl-2 was increased in LPS mice after
administration of 7,8-DHF, while ANA12 completely reversed these changes
(n=5). (H-S) The levels of p-ERK1/2, p-CaMK2, p-CREB and p-GluR1 in LPS
mice were increased after administration of 7,8-DHF, however, ANA12
reversed the effects of 7,8-DHF. There were no statistical differences
in protein levels of ERK1/2, CaMK2, CREB and GluR1 in LPS groups after
administration of 7,8-DHF or ANA12 (n=5). Data are presented as mean ±
SEM. *P < 0.05; **P < 0.01;
***P < 0.001; N.S. P > 00.5.
Figure 8. 7,8-DHF restored the LPS-induced BDNF-TrkB signaling
pathway and its downstream cascade disorder in the EC. (A-D) No
statistical difference was observed in the expression of BDNF and TrkB
in LPS mice after using 7,8-DHF or ANA12. 7,8-DHF clearly increased the
expression of p-TrkB in LPS mice, while ANA12 reversed the therapeutic
effects of 7,8-DHF (n=5). (E-G) 7,8-DHF reduced the level of Bax and
increased the level of Bcl-2 in the LPS group, however, ANA12 reversed
these changes (n=5). (H-S) The expression of p-CaMK2 and p-CREB was
increased in LPS mice after administration of 7.8-HDF, while ANA12
completely reversed the effects of 7,8-DHF. There was no significant
difference in protein levels of ERK1/2, p-ERK1/2, CaMK2, CREB, GluR1 and
p-GluR1 in LPS groups after using 7,8-DHF or ANA12 (n=5). Data are
presented as mean ± SEM. *P < 0.05; **P< 0.01; ***P < 0.001; N.S. P> 00.5.