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      Acupuncture stimulation improves scopolamine-induced cognitive impairment via activation of cholinergic system and regulation of BDNF and CREB expressions in rats

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          Abstract

          Background

          Acupuncture is an alternative therapy that is widely used to treat various neurodegenerative diseases and effectively improve cognitive and memory impairment. The aim of this study was to examine whether acupuncture stimulation at the Baihui (GV20) acupoint improves memory defects caused by scopolamine (SCO) administration in rats. We also investigated the effects of acupuncture stimulation at GV20 on the cholinergic system as well as the expression of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) in the hippocampus.

          Methods

          SCO (2 mg/kg, i.p.) was administered to male rats once daily for 14 days. Acupuncture stimulation at GV20 was performed for 5 min before SCO injection. After inducing cognitive impairment via SCO administration, we conducted a passive avoidance test (PAT) and the Morris water maze (MWM) test to assess behavior.

          Results

          Acupuncture stimulation at GV20 improved memory impairment as measured by the PAT and reduced the escape latency for finding the platform in the MWM test. Acupuncture stimulation at GV20 significantly alleviated memory-associated decreases in the levels of choline acetyltransferase (ChAT), BDNF and CREB proteins in the hippocampus. Additionally, acupuncture stimulation at GV20 significantly restored the expression of choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), BDNF and CREB mRNA in the hippocampus. These results demonstrate that acupuncture stimulation at GV20 exerts significant neuroprotective effects against SCO-induced neuronal impairment and memory dysfunction in rats.

          Conclusions

          These findings suggest that acupuncture stimulation at GV20 might be useful in various neurodegenerative diseases to improve cognitive functioning via stimulating cholinergic enzyme activities and regulating BDNF and CREB expression in the brain.

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          Most cited references60

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          The role of acetylcholine in learning and memory.

          Pharmacological data clearly indicate that both muscarinic and nicotinic acetylcholine receptors have a role in the encoding of new memories. Localized lesions and antagonist infusions demonstrate the anatomical locus of these cholinergic effects, and computational modeling links the function of cholinergic modulation to specific cellular effects within these regions. Acetylcholine has been shown to increase the strength of afferent input relative to feedback, to contribute to theta rhythm oscillations, activate intrinsic mechanisms for persistent spiking, and increase the modification of synapses. These effects might enhance different types of encoding in different cortical structures. In particular, the effects in entorhinal and perirhinal cortex and hippocampus might be important for encoding new episodic memories.
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            The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies.

            Scopolamine is used as a standard/reference drug for inducing cognitive deficits in healthy humans and animals. Effects are often interpreted in terms of a role of acetylcholine in mnemonic and/or attentional processes. In this paper an overview is given of the effects of scopolamine on animal behavior. Examination of the dose-response curve of systemically administered scopolamine indicates that sensory discrimination and attention are most sensitive to disruption. When higher doses (>0.03mg/kg) are used, deficits in other cognitive and non-cognitive functions (e.g., learning and memory, locomotor activity) are reported. Several behavioral processes (taste aversion, anxiety, short-term memory, attention) are found to be affected after intracerebral injections of scopolamine. It is concluded that effects on learning and memory performance which are observed after higher doses of scopolamine are mediated by (1) primary effects on attention and sensory/stimulus discrimination, (2) non-specific effects on behavior (e.g., locomotor activity, anxiety), and (3) peripheral side-effects (e.g., pupil dilation, salivation). Finally, the validity of scopolamine as a pharmacological model for cognitive impairment is discussed. The use of muscarinic M1 antagonists is suggested as a more selective and effective way of inducing cholinergic-induced cognitive deficits.
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              From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning.

              One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short- and long-term periods of enhanced synaptic physiology in both pre- and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.
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                Author and article information

                Contributors
                bombi@khu.ac.kr
                surzeus@naver.com
                crm04094@naver.com
                dhhahm@khu.ac.kr
                hjlee@khu.ac.kr
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                17 September 2014
                17 September 2014
                2014
                : 14
                : 1
                : 338
                Affiliations
                [ ]Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 130-701 Republic of Korea
                [ ]BK21 PLUS Korean Medicine Science Center, College of Korean Medicine, Kyung Hee University, Seoul, 130-701 Korea
                Article
                1919
                10.1186/1472-6882-14-338
                4180318
                25231482
                feb12fd9-2291-42c6-ad0a-9183d1265242
                © Lee et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 June 2014
                : 28 August 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Complementary & Alternative medicine
                scopolamine,memory,cholinergic neurons,brain-derived neurotrophic factor,camp-response element-binding protein

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