ABSTRACT
OBJECTIVE: To observe the effect of needling "Danzhong" (CV17), "Zhongwan"(CV12), "Qihai" (CV6), "Xuehai"(SP10)and "Zusanli"(ST36) (Triple Energizer Acupuncture Method) on the learning-memory ability and profile of hippocampal differentially-expressed genes and proteins of SAMP8 mice (rapid aging mice), so as to explore its underlying mechanisms in improving Alzheimer's disease (AD)．. METHODS: A total of 60 SAMP8 were used as the dementia model and randomly divided into blank control, acupoint and non-acupoint groups (n＝20 per group). The 5 acupuncture points and non-acupoints (subcostal region) on the bilateral sides were needled with filiform needles and manipulated manually for 30 s at each one，once daily, 6 times a week for 4 weeks. The Morris water maze tests (location navigation tests and space probing trials) were used to evaluate the mouse's learning-memory ability. The hippocampal tissue was extracted to detect differentially expressed genes and proteins related to acupuncture intervention by gene chip and isobaric tags for relative and absolute quantitation (iTRAQ) techniques as well as bioinformatic analysis, separately. The information is analyzed through bioinformatics database tools. Finally, immunofluorescence staining was used to verify theresults of microarray analysis. RESULTS: Compared with mice of the control and non-acupoint groups, the escape latency of location navigation task of Morris water maze tests on 4th and 5th day of training was significantly shortened in mice of the acupoint group, and the duration of stay in the original safe-platform quadrant was significantly increased in the acupoint group (P<0.05). Gene microarray displayed that in comparison with the control group, 898 differentially expressed genes were up-regulated, 418 genes were down-regulated in the hippocampus of acupoint group. The iTRAQ analysis indicated that in the acupoint and non-acupoint groups, 286 and 299 differentially expressed proteins were up-regulated, 319 and 179 proteins down-regulated, respectively. Of the 34 terms containing 47 proteins up-regulated by acupoint needling, including intermediate filament, keratin filament, myelin sheath, postsynaptic density, neuron projection were related with neurite and cytoskele-ton. While in the non-acupoint group, of the 24 terms were listed by the system, only the myelin sheath involving 11 differentially expressed proteins functions in activities of neurite and cytoskeleton. Immunofluorescence staining of the hippocampal tissue showed that the high-density distribution areas of neurons and neurite fibers were characterized by decentralization and disordering, with the highlighted areas being mainly near the cell body parts in control mice, but in mice of the acupoint group, the highlighted areas at the neurite were relatively dense, the morphology of hippocampal cells was complete, the fiber structure was clear, dense and orderly, and the neurites were closely arranged and in order, indicating an improvement of the distribution and arrangement of nerve fibers after acupuncture. The height of neurite highlight area of the acupoint group was significantly higher than that of the non-acupoint group (P<0.05)．. CONCLUSION: The "Triple Energizer Acupuncture" of acupoints is able to improve the learning-memory ability in SAMP8, which may be related to its effects in regulating the expression and function of hippocampal genes and proteins related to neurite and cytoskeleton.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate whether the antioxidation and the regulation on the Extracellular Regulated Protein Kinases (ERK) signaling pathway are involved in the protective effects of blueberry on central nervous system.</p><p><b>METHODS</b>30 Senescence-accelerated mice prone 8 (SAMP8) mice were divided into three groups and treated with normal diet, blueberry extracts (200 mg/kg•bw/day) and cyaniding-3-O-galactoside (Cy-3-GAL) (50 mg/kg•bw/day) from blueberry for 8 weeks. 10 SAMR1 mice were set as control group. The capacity of spatial memory was assessed by Passive avoidance task and Morris water maze. Histological analyses on hippocampus were completed. Malondialdehyde (MDA) levels, Superoxide Dismutase (SOD) activity and the expression of ERK were detected.</p><p><b>RESULTS</b>Both Cy-3-GAL and blueberry extracts were shown effective functions to relieve cellular injury, improve hippocampal neurons survival and inhibit the pyramidal cell layer damage. Cy-3-GAL and blueberry extracts also increased SOD activity and reduced MDA content in brain tissues and plasma, and increased hippocampal phosphorylated ERK (p-ERK) expression in SAMP8 mice. Further more, the passive avoidance task test showed that both the latency time and the number of errors were improved by Cy-3-GAL treatment, and the Morris Water Maze test showed significant decreases of latency were detected by Cy-3-GAL and blueberry extracts treatment on day 4.</p><p><b>CONCLUSION</b>Blueberry extracts may reverse the declines of cognitive and behavioral function in the ageing process through several pathways, including enhancing the capacity of antioxidation, altering stress signaling. Cy-3-GAL may be an important active ingredient for these biological effects.</p>
Subject(s)
Animals , Mice , Aging , Anthocyanins , Pharmacology , Avoidance Learning , Blueberry Plants , Chemistry , Dietary Supplements , Galactosides , Pharmacology , Hippocampus , Metabolism , Malondialdehyde , Metabolism , Maze Learning , Memory , Mitogen-Activated Protein Kinase 3 , Metabolism , Phosphorylation , Plant Extracts , Pharmacology , Superoxide Dismutase , MetabolismABSTRACT
Objective To explore the influence of Hedysari radix concentrations fluid (HRCF) on learning and memory and its effect on cerebral monoamine neurotransmitters in senescence accelerated mice. Methods The senescence accelerated mice were randomly divided into the senescence accelerated mouse/resistance 1 (SAMR1) control group, senescence accelerated mouse/prone-8 (SAMP8) model group, HRCF treatment group and aricept treatment group. After 3 months of intragastrical treatment, the learning and memory ability changes and content of norepinephrine, dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were detected respectively using Morris water maze and high performance liquid chromatography. Results In the model group, the hidden platform test indicated that the latency to find the hidden platform was remarkably prolonged, and the content of norepinephrine, dopamine, 5-hydroxytryptamine as well as 5-hydroxyindoleacetic acid were significantly reduced (P<0.01). Compared with the model group, the latency of hidden platform test was remarkably shortened (P<0.05) and the content of norepinephrine, dopamine, 5-hydroxytryptamine as well as 5-hydroxyindoleacetic acid were obviously increased in HRCF treatment group (P<0.01). Conclusion HRCF could improve learning and memory ability of SAMP8 and the influence may related to increasing the content of cerebral monoamine neurotransmitters.
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Objective To investigate the effects of an enriched environment (EE) on the psychological and behavioral symptoms of senescence and on the level of plasmic adrenocorticotropic hormone (ACTH) and serum corticosteroid (Cor). MethodsTwenty male senescence-prone SAMP8 mice of 3 months old were divided randomly into an enriched environment (EE) group and a standard environment (SE) group.Five male senescence-resistant SAMR1 mice of the same age served as the control group.Behavioral symptoms were assessed after 2 months using autonomic activity and elevated-plus maze (EPM) test performance.Plasma ACTH and serum Cor were detected using radio-immunologic methods. ResultsAverage autonomic activity frequency and EPM open-arm times were significantly lower with the SAMP8 mice than among the control group,and the autonomic activity frequency was significantly higher in the EE group than in the SE group of SAMP8 mice.The average EPM open-arm times of the EE group and the SE were not significantly different.Average ACTH and Cor levels were both significantly lower in the SAMP8 mice,and the level of ACTH was significantly higher in the EE group than in the SE group.There was no significant difference in these groups' average Cor levels. ConclusionsThe SAMP8 mice of 5 months demonstrated significant mental and behavioral abnormalities,as well as down-regulated plasma levels of ACTH and Cor.EE An enhanced environment can reduce behavioral disturbance through up-regulating ACTH.