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Tong Luo Jiu Nao ameliorates Aβ1-40-induced cognitive impairment on adaptive behavior learning by modulating ERK/CaMKII/CREB signaling in the hippocampus.

Shi Z, Lu C, Sun X, Wang Q, Chen S, Li Y, Qu L, Chen L, Bu L, Liao D, Liu X - BMC Complement Altern Med (2015)

Bottom Line: Our findings first demonstrated that TLJN can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior.Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus.TLJN can markedly enhance cognitions of Aβ1-40 microinjection animal model in adaptive behavioral tasks.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China. zhe.shield@gmail.com.

ABSTRACT

Background: Tong Luo Jiu Nao (TLJN), a modern formula of Chinese medicine extracts on the basis of Traditional Chinese Medicine theory, has been used to treat dementia. The present study aimed to investigate its ameliorating effects on Aβ1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning (RDIL) tasks, and to determine its possible mechanism of action.

Methods: Rats were pretreated with TLJN extract (0.9 and 1.8 g/kg, p.o.) for 10 daysbefore surgery, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of biochemical parameters and molecules.

Results: Our findings first demonstrated that TLJN can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus.

Conclusion: TLJN can markedly enhance cognitions of Aβ1-40 microinjection animal model in adaptive behavioral tasks. It has the potential, possibly as complementary and alternative therapy, to prevent and/or delay the deterioration of cognitive impairment in AD.

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Related in: MedlinePlus

Alteration of hippocampal acetylcholine and glutamate levels of post-training surgically manipulated animals after the behavior procedure. Subpart (A) is the content of Ach in the hippocampal; subpart (B) is the content of Glu in the hippocampal. All data are expressed as means ± SEM, n=6. Significant differences *p<0.05, **p<0.01 compared with the sham; #p<0.05, ##p<0.01 compared with the Aβ1-40.
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Fig5: Alteration of hippocampal acetylcholine and glutamate levels of post-training surgically manipulated animals after the behavior procedure. Subpart (A) is the content of Ach in the hippocampal; subpart (B) is the content of Glu in the hippocampal. All data are expressed as means ± SEM, n=6. Significant differences *p<0.05, **p<0.01 compared with the sham; #p<0.05, ##p<0.01 compared with the Aβ1-40.

Mentions: We tested neurotransmitter levels in the hippocampus after behavioral procedures were completed. Differences between groups were analyzed with one-way ANOVA. As shown in the subpart (A) of Figure 5, the TLJN min, TLJN max and DNP treated groups showed a markedly increased Ach levels in the hippocampus. The Ach level was significantly different on comparing Aβ1–40 vs. sham (F (4,26) = 2.166, p = 0.006) group. The TLJN min (p = 0.043), TLJN max (p = 0.035) and DNP (p = 0.004) treated groups showed a markedly increased Ach levels vs. Aβ1–40 group in the hippocampus. Moreover, as shown in the subpart (B) of Figure 5 the TLJN min, TLJN max and DNP treated groups showed a markedly decreased Glu levels. The Glu level was significantly different on comparing Aβ1–40 vs. sham (F (4,26) = 2.362, p = 0.017) group. The TLJN min (p = 0.020), TLJN max (p = 0.016) and DNP (p = 0.030) treated groups showed a markedly decreased Glu levels vs. Aβ1–40 group in the hippocampus.Figure 5


Tong Luo Jiu Nao ameliorates Aβ1-40-induced cognitive impairment on adaptive behavior learning by modulating ERK/CaMKII/CREB signaling in the hippocampus.

Shi Z, Lu C, Sun X, Wang Q, Chen S, Li Y, Qu L, Chen L, Bu L, Liao D, Liu X - BMC Complement Altern Med (2015)

Alteration of hippocampal acetylcholine and glutamate levels of post-training surgically manipulated animals after the behavior procedure. Subpart (A) is the content of Ach in the hippocampal; subpart (B) is the content of Glu in the hippocampal. All data are expressed as means ± SEM, n=6. Significant differences *p<0.05, **p<0.01 compared with the sham; #p<0.05, ##p<0.01 compared with the Aβ1-40.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4380248&req=5

Fig5: Alteration of hippocampal acetylcholine and glutamate levels of post-training surgically manipulated animals after the behavior procedure. Subpart (A) is the content of Ach in the hippocampal; subpart (B) is the content of Glu in the hippocampal. All data are expressed as means ± SEM, n=6. Significant differences *p<0.05, **p<0.01 compared with the sham; #p<0.05, ##p<0.01 compared with the Aβ1-40.
Mentions: We tested neurotransmitter levels in the hippocampus after behavioral procedures were completed. Differences between groups were analyzed with one-way ANOVA. As shown in the subpart (A) of Figure 5, the TLJN min, TLJN max and DNP treated groups showed a markedly increased Ach levels in the hippocampus. The Ach level was significantly different on comparing Aβ1–40 vs. sham (F (4,26) = 2.166, p = 0.006) group. The TLJN min (p = 0.043), TLJN max (p = 0.035) and DNP (p = 0.004) treated groups showed a markedly increased Ach levels vs. Aβ1–40 group in the hippocampus. Moreover, as shown in the subpart (B) of Figure 5 the TLJN min, TLJN max and DNP treated groups showed a markedly decreased Glu levels. The Glu level was significantly different on comparing Aβ1–40 vs. sham (F (4,26) = 2.362, p = 0.017) group. The TLJN min (p = 0.020), TLJN max (p = 0.016) and DNP (p = 0.030) treated groups showed a markedly decreased Glu levels vs. Aβ1–40 group in the hippocampus.Figure 5

Bottom Line: Our findings first demonstrated that TLJN can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior.Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus.TLJN can markedly enhance cognitions of Aβ1-40 microinjection animal model in adaptive behavioral tasks.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Malianwa North Road No. 151, Beijing, 100193, China. zhe.shield@gmail.com.

ABSTRACT

Background: Tong Luo Jiu Nao (TLJN), a modern formula of Chinese medicine extracts on the basis of Traditional Chinese Medicine theory, has been used to treat dementia. The present study aimed to investigate its ameliorating effects on Aβ1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning (RDIL) tasks, and to determine its possible mechanism of action.

Methods: Rats were pretreated with TLJN extract (0.9 and 1.8 g/kg, p.o.) for 10 daysbefore surgery, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of biochemical parameters and molecules.

Results: Our findings first demonstrated that TLJN can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus.

Conclusion: TLJN can markedly enhance cognitions of Aβ1-40 microinjection animal model in adaptive behavioral tasks. It has the potential, possibly as complementary and alternative therapy, to prevent and/or delay the deterioration of cognitive impairment in AD.

Show MeSH
Related in: MedlinePlus