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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

Behavioral performance in habit learning (visual signal discrimination and extinction task) in post-training surgically manipulated animals. Subpart (A) is the number of LPs per day; subpart (B) is the number of CLPs per day; subpart (C) is the number of ILPs per day; subpart (D) is the CLPR (CLP/LP) per day; subpart (E) is the number of NPs per day; subpart (F) is the number of CNPs per day; subpart (G) is the number of INPs per day; subpart (H) is the CNPR(CNP/NP). All data are expressed as means ± SEM, n=10. Significant differences *p<0.05, **p<0.01, ***p<0.001 compared with the sham; #p<0.05, ##p<0.01, ###p<0.001 compared with the Aβ1-40.
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Fig4: Behavioral performance in habit learning (visual signal discrimination and extinction task) in post-training surgically manipulated animals. Subpart (A) is the number of LPs per day; subpart (B) is the number of CLPs per day; subpart (C) is the number of ILPs per day; subpart (D) is the CLPR (CLP/LP) per day; subpart (E) is the number of NPs per day; subpart (F) is the number of CNPs per day; subpart (G) is the number of INPs per day; subpart (H) is the CNPR(CNP/NP). All data are expressed as means ± SEM, n=10. Significant differences *p<0.05, **p<0.01, ***p<0.001 compared with the sham; #p<0.05, ##p<0.01, ###p<0.001 compared with the Aβ1-40.

Mentions: As shown in Figure 4, no significant differences in NPs and CNPs were found. All parameters either increased or decreased progressively during the training days in all groups except for LPs. It demonstrated that the ability to identify an S-R association could be progressively enhanced under a stable level of lever-pressing activity. The Aβ1–40-treated group performed significant fewer CLPs, lower CLPR, CNPR and more ILPs, INPs than sham group, indicating that the Aβ1–40-administrated rats unable to adjust their responses to the cue reflecting a correct association with the reward outcome. All the drug treated groups, including TLJN min, TLJN max and DNP, displayed a marked ameliorating effect in the stage of habit learning.Figure 4


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)

Behavioral performance in habit learning (visual signal discrimination and extinction task) in post-training surgically manipulated animals. Subpart (A) is the number of LPs per day; subpart (B) is the number of CLPs per day; subpart (C) is the number of ILPs per day; subpart (D) is the CLPR (CLP/LP) per day; subpart (E) is the number of NPs per day; subpart (F) is the number of CNPs per day; subpart (G) is the number of INPs per day; subpart (H) is the CNPR(CNP/NP). All data are expressed as means ± SEM, n=10. Significant differences *p<0.05, **p<0.01, ***p<0.001 compared with the sham; #p<0.05, ##p<0.01, ###p<0.001 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

Fig4: Behavioral performance in habit learning (visual signal discrimination and extinction task) in post-training surgically manipulated animals. Subpart (A) is the number of LPs per day; subpart (B) is the number of CLPs per day; subpart (C) is the number of ILPs per day; subpart (D) is the CLPR (CLP/LP) per day; subpart (E) is the number of NPs per day; subpart (F) is the number of CNPs per day; subpart (G) is the number of INPs per day; subpart (H) is the CNPR(CNP/NP). All data are expressed as means ± SEM, n=10. Significant differences *p<0.05, **p<0.01, ***p<0.001 compared with the sham; #p<0.05, ##p<0.01, ###p<0.001 compared with the Aβ1-40.
Mentions: As shown in Figure 4, no significant differences in NPs and CNPs were found. All parameters either increased or decreased progressively during the training days in all groups except for LPs. It demonstrated that the ability to identify an S-R association could be progressively enhanced under a stable level of lever-pressing activity. The Aβ1–40-treated group performed significant fewer CLPs, lower CLPR, CNPR and more ILPs, INPs than sham group, indicating that the Aβ1–40-administrated rats unable to adjust their responses to the cue reflecting a correct association with the reward outcome. All the drug treated groups, including TLJN min, TLJN max and DNP, displayed a marked ameliorating effect in the stage of habit learning.Figure 4

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