Baicalin influences the dendritic morphology of newborn neurons in the hippocampus of chronically stressed rats

doi:10.3969/j.issn.1673-5374.2013.06.002

Abstract

Abstract:

Chronic stress models, established in adult Sprague-Dawley rats through a 14-day subcutaneous injection of 40 mg/kg corticosterone, once per day, were given a daily oral feeding of 50 mg/kg baicalin. The study was an attempt to observe the effect of baicalin on neurogenesis in chronically stressed rats. Results showed that subcutaneous injection of corticosterone significantly decreased the total number of doublecortin-positive neurons in the hippocampus. The reduced cell number caused by corticosterone was mainly due to the decrease of class II doublecortin-positive neurons, but the class I doublecortin-positive neurons were unaffected. Baicalin treatment increased the number of both class I and class II doublecortin-positive neurons. In addition, doublecortin-positive neurons showed less complexity in dendritic morphology after corticosterone injection, and this change was totally reversed by baicalin treatment. These findings suggest that baicalin exhibits a beneficial effect on adult neurogenesis.

Key words: neural regeneration, traditional Chinese medicine, neurogenesis, neurodegenerative disease, baicalin, stress, hippocampus, neurons, doublecortin, dendrites, cognition, mood regulation, grants-supported paper, photographs-containing paper, neuroregeneration

Xinghua Jiang, Junmei Xu, Dingquan Zou, Lin Yang, Yaping Wang. Baicalin influences the dendritic morphology of newborn neurons in the hippocampus of chronically stressed rats[J]. Neural Regeneration Research, 2013, 8(6): 496-505.

References

[1] Kim WR, Christian K, Ming GL, et al. Time-dependent involvement of adult-born dentate granule cells in behavior. Behav Brain Res. 2012;227(2):470-479.

[2] Tomášová L, Smajda B, Sevc J. Effects of prenatal irradiation on behaviour and hippocampal neurogenesis in adult rats. Acta Physiol Hung. 2012;99(2):126-132.

[3] van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999;2(3):266-270.

[4] Ziv Y, Ron N, Butovsky O, et al. Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci. 2006;9(2):268-275.

[5] Santarelli L, Saxe M, Gross C, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003;301(5634):805-809.

[6] Huang Z, Zhong XM, Li ZY, et al. Curcumin reverses corticosterone-induced depressive-like behavior and decrease in brain BDNF levels in rats. Neurosci Lett. 2011;493(3):145-148.

[7] Nacher J, Gomez-Climent MA, McEwen B. Chronic non- invasive glucocorticoid administration decreases polysialylated neural cell adhesion molecule expression in the adult rat dentate gyrus. Neurosci Lett. 2004;370(1):40-44.

[8] Brummelte S, Galea LA. Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats. Neuroscience. 2010;168(3):680-690.

[9] David DJ, Samuels BA, Rainer Q, et al. Neurogenesis- dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron. 2009;62(4): 479-493.

[10] Gilhooley MJ, Pinnock SB, Herbert J. Rhythmic expression of per1 in the dentate gyrus is suppressed by corticosterone: implications for neurogenesis. Neurosci Lett. 2011;489(3):177-181.

[11] Hellsten J, Wennström M, Mohapel P, et al. Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment. Eur J Neurosci. 2002;16(2):283-290.

[12] Crupi R, Mazzon E, Marino A, et al. Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice. J Pineal Res. 2010;49(2): 123-129.

[13] Yau SY, Lau BW, Tong JB, et al. Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats. PLoS One. 2011;6(9): e24263.

[14] Lau BW, Lee JC, Li Y, et al. Polysaccharides from wolfberry prevents corticosterone-induced inhibition of sexual behavior and increases neurogenesis. PLoS One. 2012;7(4):e33374.

[15] Lin B. Polyphenols and neuroprotection against ischemia and neurodegeneration. Mini Rev Med Chem. 2011;11(14): 1222-1238.

[16] Tarragó T, Kichik N, Claasen B, et al. Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor. Bioorg Med Chem. 2008;16(15):7516-7524.

[17] Tu XK, Yang WZ, Shi SS, et al. Baicalin inhibits TLR2/4 signaling pathway in rat brain following permanent cerebral ischemia. Inflammation. 2011;34(5):463-470.

[18] Zhang X, Feng G, Weng W, et al. Protective effects of baicalin and octreotide on intestinal mucosa of rats with severe acute pancreatitis. Turk J Gastroenterol. 2009; 20(2):108-115.

[19] Zhang X, Tian H, Wu C, et al. Effect of baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis. Pancreas. 2009;38(7):732-738.

[20] Liu LL, Gong LK, Wang H, et al. Baicalin protects mouse from Concanavalin A-induced liver injury through inhibition of cytokine production and hepatocyte apoptosis. Liver Int. 2007;27(4):582-591.

[21] Zeng Y, Song C, Ding X, et al. Baicalin reduces the severity of experimental autoimmune encephalomyelitis. Braz J Med Biol Res. 2007;40(7):1003-1010.

[22] Yan XH, Huang RB. Differentiation of human umbilical cord blood mesenchymal stem cells toward neurons induced by baicalin in vitro. Zhonghua Er Ke Za Zhi. 2006;44(3):214-219.

[23] Jia Y, Yang Y, Zhou Y, et al. Differentiation of rat bone marrow stromal cells into neuron induced by baicalin. Zhonghua Yi Xue Za Zhi. 2002;82(19):1337-1341.

[24] Li Y, Zhuang P, Shen B, et al. Baicalin promotes neuronal differentiation of neural stem/progenitor cells through modulating p-stat3 and bHLH family protein expression. Brain Res. 2012;1429:36-42.

[25] von Bohlen Und Halbach O. Immunohistological markers for staging neurogenesis in adult hippocampus. Cell Tissue Res. 2007;329(3):409-420.

[26] Francis F, Koulakoff A, Boucher D, et al. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron. 1999;23(2):247-256.

[27] Gleeson JG, Allen KM, Fox JW, et al. Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell. 1998;92(1):63-72.

[28] Couillard-Despres S, Winner B, Schaubeck S, et al. Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci. 2005;21(1):1-14.

[29] Rao MS, Shetty AK. Efficacy of doublecortin as a marker to analyse the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus. Eur J Neurosci. 2004;19(2):234-246.

[30] Cooper-Kuhn CM, Kuhn HG. Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain. Brain Res Dev Brain Res. 2002; 134(1-2):13-21.

[31] Wang JW, David DJ, Monckton JE, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci. 2008; 28(6):1374-1384.

[32] Komitova M, Mattsson B, Johansson BB, et al. Enriched environment increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of stroke-lesioned adult rats. Stroke. 2005;36(6):1278-1282.

[33] Valero J, España J, Parra-Damas A, et al. Short-term environmental enrichment rescues adult neurogenesis and memory deficits in APP(Sw,Ind) transgenic mice. PLoS One. 2011;6(2):e16832.

[34] Van Bokhoven P, Oomen CA, Hoogendijk WJ, et al. Reduction in hippocampal neurogenesis after social defeat is long-lasting and responsive to late antidepressant treatment. Eur J Neurosci. 2011;33(10):1833-1840.

[35] Oomen CA, Soeters H, Audureau N, et al. Severe early life stress hampers spatial learning and neurogenesis, but improves hippocampal synaptic plasticity and emotional learning under high-stress conditions in adulthood. J Neurosci. 2010;30(19):6635-6645.

[36] Brown JP, Couillard-Després S, Cooper-Kuhn CM, et al. Transient expression of doublecortin during adult neurogenesis. J Comp Neurol. 2003;467(1):1-10.

[37] Livneh Y, Mizrahi A. Long-term changes in the morphology and synaptic distributions of adult-born neurons. J Comp Neurol. 2011;519(11):2212-2224.

[38] van der Velden L, van Hooft JA, Chameau P. Altered dendritic complexity affects firing properties of cortical layer 2/3 pyramidal neurons in mice lacking the 5-HT3A receptor. J Neurophysiol. 2012;108(5):1521-1528.

[39] Sholl DA. Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat. 1953;87(4): 387-406.

[40] Li M, Tsang KS, Choi ST, et al. Neuronal differentiation of C17.2 neural stem cells induced by a natural flavonoid, baicalin. Chembiochem. 2011;12(3):449-456.

[41] Yang XS, Luo XM, Xiao B, et al. An experimental research on differentiation of mesenchymal stem cells derived from children with spinal muscular atrophy into neuron-like cells. Zhongguo Dang Dai Er Ke Za Zhi. 2007;9(5):453-456.

[42] Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature. 1997;386(6624):493-495.

[43] van Praag H, Schinder AF, Christie BR, et al. Functional neurogenesis in the adult hippocampus. Nature. 2002; 415(6875):1030-1034.

[44] Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313-1317.

[45] Gould E, Reeves AJ, Fallah M, et al. Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci U S A. 1999;96(9):5263-5267.

[46] Kornack DR, Rakic P. Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci U S A. 1999;96(10):5768-5773.

[47] Nacher J, Varea E, Blasco-Ibañez JM, et al. Expression of the transcription factor Pax 6 in the adult rat dentate gyrus. J Neurosci Res. 2005;81(6):753-761.

[48] Englund C, Fink A, Lau C, et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci. 2005;25(1):247-251.

[49] Gould E, Vail N, Wagers M, et al. Adult-generated hippocampal and neocortical neurons in macaques have a transient existence. Proc Natl Acad Sci U S A. 2001; 98(19):10910-10917.

[50] Parent JM, Yu TW, Leibowitz RT, et al. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997;17(10):3727-3738.

[51] Karl C, Couillard-Despres S, Prang P, et al. Neuronal precursor-specific activity of a human doublecortin regulatory sequence. J Neurochem. 2005;92(2): 264-282.

[52] Filippov V, Kronenberg G, Pivneva T, et al. Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci. 2003;23(3):373-382.

[53] Plümpe T, Ehninger D, Steiner B, et al. Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci. 2006;7:77.

[54] Walker TL, Yasuda T, Adams DJ, et al. The doublecortin- expressing population in the developing and adult brain contains multipotential precursors in addition to neuronal-lineage cells. J Neurosci. 2007;27(14): 3734-3742.

[55] Jung SH, Kang KD, Ji D, et al. The flavonoid baicalin counteracts ischemic and oxidative insults to retinal cells and lipid peroxidation to brain membranes. Neurochem Int. 2008;53(6-8):325-337.

[56] Liu LY, Wei EQ, Zhao YM, et al. Protective effects of baicalin on oxygen/glucose deprivation- and NMDA- induced injuries in rat hippocampal slices. J Pharm Pharmacol. 2005;57(8):1019-1026.

[57] Lee HH, Yang LL, Wang CC, et al. Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death. Brain Res. 2003; 986(1-2):103-113.

[58] Morales-Medina JC, Sanchez F, Flores G, et al. Morphological reorganization after repeated corticosterone administration in the hippocampus, nucleus accumbens and amygdala in the rat. J Chem Neuroanat. 2009;38(4):266-272.

[59] Magariños AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: comparison of stressors. Neuroscience. 1995;69(1): 83-88.

[60] Magariños AM, Orchinik M, McEwen BS. Morphological changes in the hippocampal CA3 region induced by non-invasive glucocorticoid administration: a paradox. Brain Res. 1998;809(2):314-318.

[61] Watanabe Y, Gould E, Cameron HA, et al. Phenytoin prevents stress- and corticosterone-induced atrophy of CA3 pyramidal neurons. Hippocampus. 1992;2(4): 431-435.

[62] Alfarez DN, Karst H, Velzing EH, et al. Opposite effects of glucocorticoid receptor activation on hippocampal CA1 dendritic complexity in chronically stressed and handled animals. Hippocampus. 2008;18(1):20-28.

[63] Sousa N, Lukoyanov NV, Madeira MD, et al. Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience. 2000;97(2):253-266.

[64] Magariños AM, McEwen BS. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience. 1995;69(1):89-98.

[65] Liston C, Gan WB. Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proc Natl Acad Sci U S A. 2011;108(38):16074-16079.

[66] Alfarez DN, De Simoni A, Velzing EH, et al. Corticosterone reduces dendritic complexity in developing hippocampal CA1 neurons. Hippocampus. 2009;19(9):828-836.

[67] Ishiwata H, Shiga T, Okado N. Selective serotonin reuptake inhibitor treatment of early postnatal mice reverses their prenatal stress-induced brain dysfunction. Neuroscience. 2005;133(4):893-901.

[68] Murmu MS, Salomon S, Biala Y, et al. Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy. Eur J Neurosci. 2006;24(5):1477-1487.

[69] Martínez-Téllez RI, Hernández-Torres E, Gamboa C, et al. Prenatal stress alters spine density and dendritic length of nucleus accumbens and hippocampus neurons in rat offspring. Synapse. 2009;63(9):794-804.

[70] Jia N, Yang K, Sun Q, et al. Prenatal stress causes dendritic atrophy of pyramidal neurons in hippocampal CA3 region by glutamate in offspring rats. Dev Neurobiol. 2010;70(2):114-125.

[71] Mychasiuk R, Gibb R, Kolb B. Prenatal stress alters dendritic morphology and synaptic connectivity in the prefrontal cortex and hippocampus of developing offspring. Synapse. 2012;66(4):308-314.

[72] Christian KM, Miracle AD, Wellman CL, et al. Chronic stress-induced hippocampal dendritic retraction requires CA3 NMDA receptors. Neuroscience. 2011;174:26-36.

[73] Garcia A, Steiner B, Kronenberg G, et al. Age-dependent expression of glucocorticoid- and mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus. Aging Cell. 2004;3(6):363-371.

[74] Ge QF, Hu X, Ma ZQ, et al. Baicalin attenuates oxygen-glucose deprivation-induced injury via inhibiting NMDA receptor-mediated 5-lipoxygenase activation in rat cortical neurons. Pharmacol Res. 2007;55(2):148-157.

[75] The Ministry of Science and Technology of the People’s Republic of China. Guidance Suggestions for the Care and Use of Laboratory Animals. 2006-09-30.