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

Zhe Shi,Cong Lu,Lingling Chen,Xiuping Sun,Duanfang Liao,Yinghui Li,Shanguang Chen,Qiong Wang,Xinmin Liu,Lanlan Bu,Lina Qu

doi:10.1186/s12906-015-0584-9

Abstract

BackgroundTong 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.MethodsRats 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.ResultsOur 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.ConclusionTLJN 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.

Highlights

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
Its ameliorating effects should attribute to the modulation of extracellular signal-regulated kinase (ERK)/ calmodulin-dependent protein kinase II (CaMKII)/cAMP response element-binding protein (CREB) signaling in the hippocampus
The present study extended our previous work in the utilization of the novel series of reward-directed instrumental learning (RDIL) tasks in efficacy evaluation with two significant findings: one is that chronic TLJN (0.9 and 1.8 g/kg, p.o.) treatment improved cognition on RDIL in Amyloid β Protein Fragment 1–40 (Aβ1–40) manipulated rats; the other is that its therapeutic effects could attribute to the enhancement of memory-related molecules in the hippocampus

Summary

Introduction

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. A feasible method for detecting this pivotal aspect of cognition would contribute to a more comprehensive understanding of the drugs in preclinical research Based on this consideration, our laboratory recently introduced a series of reward-directed instrumental learning (RDIL) tasks for studying cognitions in adaptive behavior [6,7]. Instrumental conditioning, which is called operant conditioning, is a form of associative learning through which an animal learns to modify its behavior from the foreseeable consequences [8]. It is one of the most elementary forms of adaptive behavior [9] and reflects the remarkable aspects of ability that reaches its highest form in human beings [10]. This flexibility allows rapid behavioral alterations in the face of changing consequences, conferring a survival advantage [11]

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