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Cynomorium songaricum extract enhances novel object recognition, cell proliferation and neuroblast differentiation in the mice via improving hippocampal environment
© Yoo et al.; licensee BioMed Central Ltd. 2014
Received: 9 September 2013
Accepted: 31 December 2013
Published: 7 January 2014
Cynomorium songaricum Rupr. (CS) has been used as a medicine to treat many diseases as well as to alleviate age-related issues, such as memory impairment, dementia, and stress. In this study, we assessed the effects of Cynomorium songaricum extract (CSE) on the novel object recognition, cell proliferation and neuroblast differentiation in the dentate gyrus of mice by using 5-bromodeoxyuridine (BrdU) and polysialylated neural cell adhesion molecule (PSA-NCAM). We also measured serum corticosterone levels to assess its correlation with neurogenesis and stress.
Male C57BL/6 J mice were divided into 3 groups: vehicle-treated, 40 mg/kg CSE-treated, and 100 mg/kg CSE-treated. The vehicle and CSE were given to mice once a day for 3 weeks. BrdU was injected twice a day for 3 days to label newly generated cells.
Administration of CSE significantly increased the preferential exploration of new objects in these mice. In addition, administration of CSE decreased serum levels of corticosterone. BrdU-positive cells as well as brain-derived neurotrophic factor (BDNF) mRNA expression in the dentate gyrus were higher in the CSE-treated groups than in the vehicle-treated group. PSA-NCAM-positive neuroblasts and their well-developed tertiary dendrites were also significantly increased by the treatment of CSE. These effects were prominent at the higher dosage than at the lower dosage.
These results suggest that administration of CSE increases cell proliferation and neuroblast differentiation in the dentate gyrus of mice by reducing serum corticosterone levels and increasing BDNF levels in this area.
Findings of recent research suggest that neurogenesis occurs throughout the lifetime in the adult mammalian brain [1–4]. There are 2 discrete neurogenic regions in the adult brain; the dentate gyrus is one of them . The dentate gyrus is closely related to learning and memory [6, 7], and it has been reported that hippocampal neurogenesis is associated with neurological problems, such as depression and Alzheimer’s disease [8, 9]. In the dentate gyrus, new neurons are produced from progenitor cells in the subgranular zone and migrate into the granule cell layer . Neurogenesis in the adult dentate gyrus is highly labile  and is affected by many exogenous and endogenous factors [11, 12].
Cynomorium songaricum Rupr. (CS) is a well-known root-parasitic plant and is distributed throughout northwest China . Cynomorium songaricum extract (CSE) has been widely used as Chinese herbal remedy for problems such as sexual dysfunction, renal disease, and lumbar weakness . Moreover, it has been reported that CS induces proliferation of undifferentiated spermatogonia with glial cell-derived neurotrophic factor (GDNF) enhancement . Chemically, CS consists of organic acids, triterpenes, polysaccharides, steroidal compounds, and flavonoids . CSE has been shown to suppress age-related learning impairments in aged flies by reducing hydroperoxide levels and increasing antioxidants . Among the chemical compounds in CS, flavonoids have antioxidant effects, and certain types of flavonoids are involved in neuroprotection and hippocampal neurogenesis [17–19]. It has also been reported that CSE modulates γ-aminobutyric acid (GABA) and monoamine transporters, both of which are involved in hippocampal neurogenesis .
Novel object recognition tasks are non-aversive learning paradigms, which rely on spontaneous exploratory behavior in experimental animals. Therefore, we investigated the effects of CSE on novel object recognition and hippocampal neurogenesis by using 5-bromodeoxyuridine (BrdU) for cell proliferation and polysialylated neural cell adhesion molecule (PSA-NCAM) for detecting developing granule neurons in mice. We also measured serum corticosterone and brain-derived neurotrophic factor (BDNF) mRNA expression levels to elucidate the possible effect of CSE on neurogenesis.
Preparation of CSE
Cynomorium songaricum Rupr. was purchased from Kyung-dong market (Seoul, South Korea). The plants were authenticated by two oriental medical doctors and the voucher specimen was deposited in our laboratory (deposition number: 2012–028). The plants (100 g) were chopped and blended using a blender and soaked in 2 L of 80% ethanol and refluxed at 20°C for 2 h three times. The insoluble materials were removed through centrifugation at 10,000 × g for 30 min, and the resulting supernatant was concentrated and freeze-dried to yield a powder (yield: 13.2%). Before each experiment, the dried extract was dissolved in distilled and deionized water.
The progeny of male C57BL/6 J mice were purchased from the Jackson Laboratory Co. Ltd (Bar Harbor, ME). Six-week-old mice were used in this study. The mice were housed in a conventional state under adequate controlled temperature (22°C), humidity (55%), 12-h light/ 12-h dark cycle, and provided with free access to food and tap water. The procedures for the care and handling of animals conformed to guidelines that are in compliance with current international laws and policies (NIH Guide for the Care and Use of Laboratory Animals, NIH Publication No. 85–23, 1985, revised 1996), and the experimental protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Seoul National University (approval no. SNU-110527-2). All of the experiments were conducted in a way as to minimize the number of animals used and the suffering caused by the procedures used in the present study.
Treatment with CSE and BrdU
Mice were randomly divided into the 3 groups: vehicle-treated group, 40 and 100 mg/kg CSE-treated groups (n = 12 in each group). Vehicle or CSE were orally administered to mice using a feeding needle once a day for 21 days and the animals were sacrificed at immediately after the novel object recognition test. These schedules were adopted because PSA-NCAM is a marker for differentiated neuroblasts expressed in immature neurons from only 1 to 21 days of cell age. In order to determine the integration of new neurons generated in the adult brain, the animals in the vehicle-treated group (n = 7) and the 40/100 mg/kg CSE-treated groups (n = 7 in each group) were treated with 50 mg/kg 5-bromodeoxyuridine (BrdU, Sigma, St. Louis, MO) twice a day for 3 days from the day of the first CSE treatment.
Novel object recognition test
Blood sampling and measurement of corticosterone levels
For blood sampling, the animals (n = 12 in each group) were anesthetized with intraperitoneal injection of 1 g/kg urethane (Sigma, St. Louis, MO), and blood samples were collected from each mouse by cardiac puncture before tissue sampling for immunohistochemistry and PCR analysis. Serum was separated from the blood by centrifugation at 1,100 g for 15 min at 4°C and serum (50 μL) was added to 5 mL of methylene chloride and incubated at room temperature for 10 min. After filtration with cheesecloth, the mixture was combined with 2.5 mL of fluorescence reagent (7:3, sulfuric acid/absolute ethanol), vortexed vigorously and incubated for 30 min at room temperature. After centrifugation, the lower layer was measured using a spectrophotometer (excited wavelength, 475 nm; emission wavelength, 530 nm).
Tissue processing for histology
For histology, the animals (n = 7 in each group) were used after blood sampling. The animals were perfused transcardially with 0.1 M phosphate-buffered saline (PBS, pH 7.4) followed by 4% paraformaldehyde in 0.1 M phosphate-buffer. The brains were removed and postfixed in the same fixative for 4 h. The brain tissues were cryoprotected by infiltration with 30% sucrose overnight. Thirty-μm-thick brain sections in coronal plane were serially cut using a cryostat (Leica, Wetzlar, Germany). The sections were collected into six-well plates containing PBS for further process.
Immunohistochemistry for BrdU and PSA-NCAM
To obtain the accurate data for immunohistochemistry, the free-floating sections were carefully processed under the same conditions. The tissue sections were selected between −1.46 mm and −2.46 mm posterior to the bregma in reference to the mouse atlas for each animal . The sections were sequentially treated with 0.3% hydrogen peroxide (H2O2) in PBS for 30 min and 10% normal goat serum in 0.05 M PBS for 30 min. For BrdU immunostaining, DNA was first denatured by incubating the sections in 50% formamide/2× standard saline citrate at 65°C for 2 h and in 2 N HCL at 37°C for 30 min. They were next incubated with diluted mouse anti-PSA-NCAM (1:200; Chemicon, Temecula, CA) or rat anti-BrdU (1:200, BioSource International, Camarillo, CA) overnight at room temperature and subsequently exposed to biotinylated goat anti-mouse IgG (1:200; Vector, Burlingame, CA) or FITC-conjugated anti-rat IgG (1:200; Jackson ImmunoResearch, West Grove, PA). For PSA-NCAM staining, the sections were incubated with streptavidin peroxidase complex (1:200; Vector), visualized with reaction to 3,3’-diaminobenzidinetetrachloride (Sigma, St. Louis, MO) in 0.1 M Tris–HCl buffer (pH 7.2) and mounted on gelatin-coated slides.
In order to quantitatively analyze BrdU- and PSA-NCAM-positive cells, 10 sections per animal selected in the hippocampus at the level of −1.46 to −2.46 mm posterior to the Bregma. BrdU- and PSA-NCAM-positive cells were calculated using an image analyzing system equipped with a computer-based CCD camera (software: Optimas 6.5, CyberMetrics, Scottsdale, AZ). The cell counts from all of the sections of all of the mice were averaged.
BDNF mRNA levels in the dentate gyrus
For PCR analysis, the animals (n = 5 in each group) were used in this study after blood sampling. The dentate gyrus was dissected out from brain tissues. RNA extraction was performed using a total RNA isolation kit (Macherney-Nagel). Spectrophotometric measurements were conducted using the Nanodrop Spectrophotometer (Nanodrop Technologies Wilmington, DE, USA) to determine RNA concentration and purity. A high capacity cDNA archive kit (Applied Biosystems) was used to reverse transcribe the equalized RNA samples. Quantitative real-time PCR (qPCR) was performed with 50 ng cDNA using custom-designed gene-expression assays for BDNF.
Gene expression of targets was assessed using Taqman gene expression assays (Applied Biosystems, UK) containing specific target primers, and FAM-labeled MGB target probes. β-actin gene expression was used to normalize gene expression between samples, and was quantified using a β-actin endogenous control gene expression assay containing specific primers, and a VIC-labeled MGB probe for rat β-actin. Analysis was performed using the ΔΔCT method. The primers used were as follows: 5′-GTGACAGTATTAGCGAGTGGG −3′ (forward) and 5′-CTAGGGCGGCCCACGATGGA-3′ (reverse) for BDNF and 5’-GCACCACACCTTCTA CAATG-3′ (forward) and 5′-TGCTTGCTGATCCACATCTG-3′ (reverse) for β-actin.
The data shown here represent the means of experiments performed for each experimental area. Differences among the means were statistically analyzed by one-way analysis of variance followed by Tukey’s multiple range method in order to elucidate differences between the vehicle- and CSE-treated groups.
Effects of CSE on object recognition
Effects of CSE on serum corticosterone levels
Effects of CSE on cell proliferation
Effects of CSE on neuroblast differentiation
Effects of CSE on BDNF mRNA expression
In the present study, we observed the behavioral preferences of mice to novel objects after CSE treatment; this behavioral paradigm exploits the ability of the mice to explore novel objects over familiar ones during simultaneous presentation and has been employed to evaluate recognition memory . During training periods, mice in all groups did not show any preferences among the 3 different objects. However, during the test periods, CSE-treated mice showed strong preferences for the novel object, while vehicle-treated mice displayed a much lesser preference for it. The result of the behavioral test is supported by changes of serum corticosterone and BDNF expression measured in this study.
We checked serum corticosterone and BDNF mRNA levels to elucidate the possible mechanisms for hippocampal neurogenesis. CSE treatment decreased serum corticosterone levels in general, and the corticosterone level in the 100 mg/kg CSE-treated group was lower than that in the 40 mg/kg CSE-treated group. It has been reported that corticosteroid hormones regulate the proliferation, survival, and death of granule cells in the dentate gyrus [22–24]. Additionally, corticosterone is known to be associated with cognitive impairment and has detrimental effects on LTP in the dentate gyrus [25–27]. Moreover, corticosterone acts on hippocampal BDNF expression through the exon IV promoter , which is required for the enhancement of hippocampal neurogenesis .
Next, we morphologically observed the effects of CSE on cell proliferation and neuroblast differentiation in the dentate gyrus. Treatment with CSE increased both BrdU-positive cells and PSA-NCAM-positive neuroblasts. These neuroblasts displayed well-developed dendrites, indicating that CSE may be involved in neuroblast maturation. Therefore, treatment with CSE can possibly modulate synaptic plasticity by increasing cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus. It has been reported that functional and morphological changes in the synapse induce altered neuronal plasticity in the mammalian brain [30, 31]. Additionally, CSE is known to act as an inhibitor of serotonin and GABA transporters, both of which are crucial for limiting monoaminergic and GABAergic activity [13, 32, 33]. GABA is the principal inhibitory neurotransmitter in the brain and plays an important role in CNS development and plasticity , and serotonin is an important modulator of hippocampal neurogenesis . GABA also significantly increases recognition and working memory in rats .
Administration of CSE significantly increased BDNF mRNA expression in the dentate gyrus homogenates. BDNF, synthesized locally in the dendrites of granule cells, promotes differentiation and maturation of progenitor cells in the subgranular zone of dentate gyrus by enhancing GABA release . Here, the increase of tertiary dendrites of the neuroblasts, stained with PSA-NCAM, may be associated with BDNF increase in the dentate gyrus.
Recently, many researchers have explored the mechanism of action and function of CSE in the brain. CSE has been shown to attenuate Aβ-induced cell death and protect against superoxide anion-induced cell death [38, 39]. In addition, CSE exhibits anti-aging effects by increasing telomere length in the brain of the D-galactose-induced aging mice . In this study, we confirmed that CSE administration influences hippocampal neurogenesis and cognitive memory by changing BDNF and serum corticosterone levels.
Treatment with CSE significantly increased preference for the novel object in the novel object recognition test and enhanced hippocampal neurogenesis in the mouse dentate gyrus. Changes of the BDNF and serum corticosterone levels were also detected and may be closely associated with novel object recognition and hippocampal neurogenesis. These results suggest that CSE has the potential for enhancing hippocampal plasticity and can be used to people who have problems in hippocampal memory.
This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2011–0013933).
- Paizanis E, Kelai S, Renoir T, Hamon M, Lanfumey L: Life-long hippocampal neurogenesis: environmental, pharmacological and neurochemical modulations. Neurochem Res. 2007, 32: 1762-1771. 10.1007/s11064-007-9330-0.View ArticlePubMedGoogle Scholar
- Gage FH: Mammalian neural stem cells. Science. 2000, 287: 1433-1438. 10.1126/science.287.5457.1433.View ArticlePubMedGoogle Scholar
- Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH: Neurogenesis in the adult human hippocampus. Nat Med. 1998, 4: 1313-1317. 10.1038/3305.View ArticlePubMedGoogle Scholar
- Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E: Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci USA. 1999, 96: 5263-5267. 10.1073/pnas.96.9.5263.View ArticlePubMedPubMed CentralGoogle Scholar
- Sohur US, Emsley JG, Mitchell BD, Macklis JD: Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells. Philos Trans R Soc Lond B Biol Sci. 2006, 361: 1477-1497. 10.1098/rstb.2006.1887.View ArticlePubMedGoogle Scholar
- Garthe A, Behr J, Kempermann G: Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS One. 2009, 4: e5464-10.1371/journal.pone.0005464.View ArticlePubMedPubMed CentralGoogle Scholar
- Deng W, Aimone JB, Gage FH: New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?. Nat Rev Neurosci. 2010, 11: 339-350. 10.1038/nrn2822.View ArticlePubMedPubMed CentralGoogle Scholar
- Sahay A, Hen R: Hippocampal neurogenesis and depression. Novartis Found Symp. 2008, 289: 152-160.View ArticlePubMedGoogle Scholar
- Mu Y, Gage FH: Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener. 2011, 6: 85-10.1186/1750-1326-6-85.View ArticlePubMedPubMed CentralGoogle Scholar
- Gould E, Cameron HA, Daniels DC, Woolley CS, McEwen BS: Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci. 1992, 12: 3642-3650.PubMedGoogle Scholar
- Lee E, Son H: Adult hippocampal neurogenesis and related neurotrophic factors. BMB Rep. 2009, 42: 239-244. 10.5483/BMBRep.2009.42.5.239.View ArticlePubMedGoogle Scholar
- Van Praag H, Kempermann G, Gage FH: Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999, 2: 266-270. 10.1038/6368.View ArticlePubMedGoogle Scholar
- Zhao G, Wang J, Qin GW, Guo LH: Cynomorium songaricum extracts functionally modulate transporters of γ-aminobutyric acid and monoamine. Neurochem Res. 2010, 35: 666-676. 10.1007/s11064-009-0118-2.View ArticlePubMedGoogle Scholar
- Liu HP, Chang RF, Wu YS, Lin WY, Tsai FJ: The yang-tonifying herbal medicine Cynomorium songaricum extends lifespan and delays aging in Drosophila. Evid Based Complement Alternat Med. 2012, 2012: 735481-PubMedPubMed CentralGoogle Scholar
- Yang WM, Kim HY, Park SY, Kim HM, Chang MS, Park SK: Cynomorium songaricum induces spermatogenesis with glial cell-derived neurotrophic factor (GDNF) enhancement in rat testes. J Ethnopharmacol. 2010, 128: 693-696. 10.1016/j.jep.2010.02.020.View ArticlePubMedGoogle Scholar
- Jiang ZH, Tanaka T, Sakamoto M, Jiang T, Kouno I: Studies on a medicinal parasitic plant: lignans from the stems of Cynomorium songaricum. Chem Pharm Bull. 2001, 49: 1036-1038. 10.1248/cpb.49.1036.View ArticlePubMedGoogle Scholar
- Yu FR, Liu Y, Cui YZ, Chan EQ, Xie MR, McGuire PP, Yu FH: Effects of a flavonoid extract from Cynomorium songaricum on the swimming endurance of rats. Am J Chin Med. 2010, 38: 65-73. 10.1142/S0192415X10007774.View ArticlePubMedGoogle Scholar
- Lee S, Kim DH, Lee DH, Jeon SJ, Lee CH, Son KH, Jung JW, Shin CY, Ryu JH, Oroxylin A: A flavonoid, stimulates adult neurogenesis in the hippocampal dentate gyrus region of mice. Neurochem Res. 2010, 35: 1725-1732. 10.1007/s11064-010-0235-y.View ArticlePubMedGoogle Scholar
- Gutierrez-Merino C, Lopez-Sanchez C, Lagoa R, Samhan-Arias AK, Bueno C, Garcia-Martinez V: Neuroprotective actions of flavonoids. Curr Med Chem. 2011, 18: 1195-1212. 10.2174/092986711795029735.View ArticlePubMedGoogle Scholar
- Franklin KBJ, Paxinos G: The Mouse Brain in Stereotaxic Coordinates. 1997, San Diego: Academic PressGoogle Scholar
- Ennaceur A, Delacour J: A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res. 1988, 31: 47-59. 10.1016/0166-4328(88)90157-X.View ArticlePubMedGoogle Scholar
- Sloviter RS, Valiquette G, Abrams GM, Ronk EC, Sollas AL, Paul LA, Neubort S: Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science. 1989, 243: 535-538. 10.1126/science.2911756.View ArticlePubMedGoogle Scholar
- Montaron MF, Piazza PV, Aurousseau C, Urani A, Le Moal M, Abrous DN: Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity. Eur J Neurosci. 2003, 18: 3105-3111. 10.1111/j.1460-9568.2003.03048.x.View ArticlePubMedGoogle Scholar
- Lee CH, Yoo DY, Park OK, Park JH, Yi SS, Yoon YS, Won MH, Hwang IK: Effects of adrenalectomy and replacement therapy of corticosterone on cell proliferation and neuroblast differentiation in the rat dentate gyrus. Neurochem Res. 2011, 36: 1767-1775. 10.1007/s11064-011-0492-4.View ArticlePubMedGoogle Scholar
- Kalminjn S, Launer LJ, Stolk RP, DeJong FJ, Pols HAP, Hofman A, Breteler MMB, Lamberts SWJ: A prospective study of cortisol, dehydroepiandrosterone sulfate and cogntiive function in the elderly. J Clin Endocrinol Metab. 1998, 83: 3487-3492. 10.1210/jc.83.10.3487.View ArticleGoogle Scholar
- Van Niekerk JK, Huppert FA, Herbert J: Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation. Psychoneuroendocrinology. 2001, 26: 591-612. 10.1016/S0306-4530(01)00014-2.View ArticlePubMedGoogle Scholar
- Kaminska M, Harris J, Gijsbers K, Dubrovsky B: Dehydroepiandrosterone sulfate (DHEAS) counteracts decremental effects of corticosterone on dentate gyrus LTP. Implications for depression. Brain Res Bull. 2000, 52: 229-234. 10.1016/S0361-9230(00)00251-3.View ArticlePubMedGoogle Scholar
- Hansson AC, Sommer WH, Metsis M, Strömberg I, Agnati LF, Fuxe K: Corticosterone actions on the hippocampal brain-derived neurotrophic factor expression are mediated by exon IV promoter. J Neuroendocrinol. 2006, 18: 104-114. 10.1111/j.1365-2826.2005.01390.x.View ArticlePubMedGoogle Scholar
- Rossi C, Angelucci A, Costantin L, Braschi C, Mazzantini M, Babbini F, Fabbri ME, Tessarollo L, Maffei L, Berardi N, Caleo M: Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci. 2006, 24: 1850-1856. 10.1111/j.1460-9568.2006.05059.x.View ArticlePubMedGoogle Scholar
- Burke SN, Barnes CA: Senescent synapses and hippocampal circuit dynamics. Trends Neurosci. 2010, 33: 153-161. 10.1016/j.tins.2009.12.003.View ArticlePubMedPubMed CentralGoogle Scholar
- Schimanski LA, Barnes CA: Neural protein synthesis during aging: effects on plasticity and memory. Front Aging Neurosci. 2010, 2: 26-PubMedPubMed CentralGoogle Scholar
- Hersch SM, Yi H, Heilman CJ, Edwards RH, Levey AI: Subcellular localization and molecular topology of the dopamine transporter in the striatum and substantia nigra. J Comp Neurol. 1997, 388: 211-227. 10.1002/(SICI)1096-9861(19971117)388:2<211::AID-CNE3>3.0.CO;2-4.View ArticlePubMedGoogle Scholar
- Nelson N: The family of Na+/Cl- neurotransmitter transporters. J Neurochem. 1998, 71: 1785-1803.View ArticlePubMedGoogle Scholar
- Asada H, Kawamura Y, Maruyama K, Kume H, Ding RG, Kanbara N, Kuzume H, Sanbo M, Yagi T, Obata K: Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci USA. 1997, 94: 6496-6499. 10.1073/pnas.94.12.6496.View ArticlePubMedPubMed CentralGoogle Scholar
- Xia L, Delomenie C, David I, Rainer Q, Marouard M, Delacroix H, David DJ, Gardier AM, Guilloux JP: Ventral hippocampal molecular pathways and impaired neurogenesis associated with 5-HT1A and 5-HT1B receptors disruption in mice. Neurosci Lett. 2012, 521: 20-25. 10.1016/j.neulet.2012.05.046.View ArticlePubMedGoogle Scholar
- Thanapreedawat P, Kobayashi H, Inui N, Sakamoto K, Kim M, Yoto A, Yokogoshi H: GABA affects novel object recognition memory and working memory in rats. J Nutr Sci Vitaminol. 2013, 59: 152-157. 10.3177/jnsv.59.152.View ArticlePubMedGoogle Scholar
- Waterhouse EG, An JJ, Orefice LL, Baydyuk M, Liao GY, Zheng K, Lu B, Xu B: BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission. J Neurosci. 2012, 32: 14318-14330. 10.1523/JNEUROSCI.0709-12.2012.View ArticlePubMedPubMed CentralGoogle Scholar
- Lu Y, Wang Q, Melzig MF, Jenett-Siems K: Extracts of Cynomorium songaricum protect human neuroblastoma cells from beta-amyloid25-35 and superoxide anion induced injury. Pharmazie. 2009, 64: 609-612.PubMedGoogle Scholar
- Liu Y, Li H, Wang X, Zhang G, Wang Y, Di D: Evaluation of the free radical scavenging activity of Cynomorium songaricum Rupr. by a novel DPPH-HPLC method. J Food Sci. 2011, 76: C1245-C1249. 10.1111/j.1750-3841.2011.02392.x.View ArticlePubMedGoogle Scholar
- Ma L, Chen G, Nie L, Ai M: Effect of Cynomorium songaricum polysaccharide on telomere length in blood and brain of D-galactose-induced senescence mice. Zhongguo Zhong Yao Za Zhi. 2009, 34: 1257-1260.PubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/14/5/prepub
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