ABSTRACT Ferulic acid (FA) is a ubiquitous phenolic acid of low toxicity, and sodium ferulate (SF) is its sodium salt. Our previous studies have revealed that FA shows neuroprotective effect and significant antidepressant- like effect. The aim of this study was to investigate its potential neurogenesis-enhancing effect and its role in repair following stress-induced neuronal damage. MTT assay was performed to measure the effect of SF on the growth of rat pheochromocytoma (PC12) cells; morphological and immunocytochemical meth- ods were used for assessing its differentiation-induc- ing action. Chronic mild stress (CMS) tests were per- formed to establish rat model of depression. The histopathology of animal brains was studied to ana- lyze CMS-induced morphological changes and the effect of SF on the repair of CMS-induced brain in- jury. The expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and the proliferation of neural stem cell/neural progenitor cells were assessed in the hippocampi of chronic mild stress (CMS)-induced depression-like model rats by immunohistochemistry and bromodeoxyuridine (BrdU)- incorporation assays, respectively. Our in vitro tests showed that SF promoted the proliferation of PC12 cells in the concentration range of 5 - 320 μM, and induced PC12 cells to differentiate to more mature cells with the morphological characteristics and mo- lecular marker of neuronal-like cells. In vivo tests showed that SF up-regulated the expressions of NGF and BDNF, and induced the proliferation of neural stem cell/neural progenitor cells in the hippocampi of CMS-induced depression-like model rats. This study provides evidences that SF shows neurogenesis-en- hancing effect, and its antidepressant-like effect of SF may be related directly and closely to its above-men- tioned effect.
Cite this paper
nullYu, L. , Zhang, Y. , Liao, M. , Wang, Y. , Ma, R. , Zhang, X. and Yu, T. (2011) Neurogenesis-enhancing effect of sodium ferulate and its role in repair following stress-induced neuronal damage. World Journal of Neuroscience, 1, 9-18. doi: 10.4236/wjns.2011.12002.
 Mao, Q.Q., Ip, S.P., Ko, K.M., Tsai, S.H., Zhao, M. and Che, C.T. (2009) Peony glycosides protect against corticos-terone-induced neurotoxicity in PC12 Cells. Cellular and Molecular Neurobiology, 29, 643-647.
Sapolsky, R.M. (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Archives of Gene- ral Psychiatry, 57, 925-935.
Magarinos, A.M., McEwen, B.S., Flugge, G. and Fuchs, E. (1996) Chronic psychosocial stress caused apical den- dritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. The Journal of Neuroscience, 16, 3534-3540.
Eriksson, P.S., Perfilieva, E., Bj?rk-Eriksson, T., Alborn, A.M., Nordborg, C., Peterson, D.A. and Gage, F.H. (1998) Neurogenesis in the adult human hippocampus. Nature Medicine, 4, 1313-1317. doi:10.1038/3305
Jacobs, B.L. (2002) Adult brain neurogenesis and de- pression. Brain, Behavior, and Immunity, 16, 602-609.
Ji, Y.B. (1999) Pharmacological action and application of blood-activating and stasis-eliminating available compo- sition of traditional Chinese medicine. Heilongjiang Sci- ence and Technique Press, Harbin, 118-121.
Jing, H., Yao, L.Y., Li, J.S., Song, Y.Q. and Chao, W. (2002) Research progress of pharmacology of sodium ferulate. Northwest Pharmaceutical Journal, 17, 236-238.
Grafe, E. (1992) Antioxidant potential of ferulic acid. Free Radical Biology and Medicine, 13, 435-448.
Scott, B.C., Butler, J., Halliwell, B. and Aruoma, O.I. (1993) Evaluation of the antioxidant actions of ferulic acid and catechins. Free Radical Research, 19, 241-253.
Fernandez, M.A., Saenz, M.T. and Garcia, M.D. (1998) Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens. Journal of Pharmacy and Pharmacology, 50, 1183-1186.
Ozaki, Y. (1992) Antiinflammatory effect of tetramethyl- pyrazine and ferulic acid. Chemical & Pharmaceutical Bulletin, 40, 954-956.
Suzuki, A., Kagawa, D., Ochiai, R., Tokimitsu, I. and Saito, I. (2002a) Green coffee bean extract and its metabolites have a hypotensive effect in spontaneously hypertensive rats. Hypertension Research, 25, 99-107.
Suzuki, A., Kagawa, D., Fujii, A., Ochiai, R., Tokimitsu, I. and Saito, I. (2002b) Short- and long-term effects of ferulic acid on blood pressure in spontaneously hyper- tensive rats. American Journal of Hypertension, 15, 351- 357.
Zhang, Y.P., Yu, L.J., Wang, Y.P., Liao, M.N., Ma, R.D., Zhang, X.Y. and Yu, T.X. (2011) Neuroprotective` effects of sodium ferulate and its antidepressant-like effect measured by acute and chronic experimental method in animal model of depression. Journal of Behavioral and Brain Science, 1, 37-46.
Yu, T.X., Zhao, Y., Shi, W.C., Ma, R.D. and Yu, L.J. (1997) Effects of maternal oral administration of mono- sodium glutamate at a late stage of pregnancy on developing mouse fetal brain. Brain Research, 747, 195-206.
Yu, L.J., Zhang, Y.P., Ma, R.D., Bao, L., Fang, J.Z. and Yu, T.X. (2006) Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. European Neuropsycho- pharmacology, 16, 170-177.
Zhang, Y.P., Yu, L.J., Ma, R.D., Bao, L., Zeng, R., Fang, J.Z., Zhang, X.Y. and Yu, T.X. (2008a) Potent protective effect of ferulic acid on glutamate-induced neurotoxicity in adult mice. Chinese Journal of Neuromedicine, 7, 596-599.
Yang, P.P., Yu, L.J., Ma, R.D., Zhang, Y.P., Zhang, X.Y. and Yu, T.X. (2008) Intracerebroventricularly administered sodium ferulate-mediateed brain repair following glutamate-induced exitotoxic neuronal damage in adult mice. Chinese Journal of Behavioral Medical Science, 17, 13-15.
Zhang, Y.P., Yu, L.J., Ma, R.D., Zhang, X.Y. and Yu, T.X. (2008b) Effects of administered sodium ferulate on the repair of glutamate-induced excitotoxic neuronal impair in mouse fetal brain. Chinise Journal of Behavioral Medical Science, 17, 968-971.
Shafer, T.J. and Atchison, W.D. (1991) Transmitter, ion channel and receptor properties of pheochromocytoma (PC12) cells: A model for neurotoxicological studies. Neurotoxicology, 12, 473-492.
Yoshizumi, M., Kogame, T., Suzaki, Y., Fujita, Y., Kyaw, M., Kirima, K., Ishizawa, K., Tsuchiya, K., Kagami, S. and Tamaki, T. (2002) Ebselen attenuates oxidative stress-induced apoptosis via the inhibition of the c-Jun N-terminal kinase and activator protein-1 signalling pathway in PC12 cells. British Journal of Pharmacology, 136, 1023-1032.
Hansen, M.B., Nielsen, S.E. and Berq, K. (1989) Re- examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. Journal of Immunological Methods, 119, 203-210.
Dagai, L., Peri-Naor, R. and Birk, R.Z. (2009) Docosahexaenoic acid significantly stimulates immediate early response genes and neurite outgrowth. Neurochemical Research, 34, 867-75. doi:10.1007/s11064-008-9845-z
Julien J.P. and Mushynski W.E. (1998) Neurofilaments in health and disease. Progress in Nucleic Acid Research and Molecular Biology, 61, 1-23.
Ali, H., Jurga, M., Kurgonaite, K., Forraz, N. and McGuckin, C. (2009) Defined serum-free culturing conditions for neural tissue engineering of human cord blood stem cells. Acta Neurobiologiae Experimentalis, 69, 11-23.
Guzen, F.P., De Almeida Leme, R.J., De Andrade, M.S., de Luca, B.A. and Chadi, G. (2009) Glial cell line- derived neuro-trophic factor added to a sciatic nerve fragment grafted in a spinal cord gap ameliorates motor impairments in rats and increases local axonal growth. Restorative Neurology and Neuroscience, 27, 1-16.
Willner, P., Towell, A., Sampson, D., Sophokleous, S. and Muscat, R. (1987) Reduction of sucrose preference by chronic un- predictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology, 93, 358-364.
Moreau, J.L., Jenck, F., Martin, J.R., Mortas, P. and Haefely, W.E. (1992) Antidepressant treatment prevents chronic unpredictabl mild stress-induced anhedonia as assessed by ventral tegmentum self-stimulation behavior in rats. European Neuropsychopharmacology, 2, 43-49.
Shi, Z.R., Itzkowitz, S.H. and Kim, Y.S. (1988) A comparison of three immunoperoxidase techniques for antigen detection in colorectal carcinoma tissues. Journal of Histochemistry & Cytochemistry, 36, 317-322.
Chen, J.Q., Zhan, W.H., He, Y.L., Peng, J.S., Wang, J.P., Cai, S.R. and Ma, J.P. (2004) Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas. World Journal of Gastroenterology, 10, 776-782.
Malberg, J.E., Eisch, A.J., Nestler, E.J. and Duman, R.S. (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. The Journal of Neuroscience, 20, 9104-9110.
Parent, J., Yu, T., Leibowitz, R., Geschwind, D., Sloviter, R. and Lowenstein, D. (1977) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant net-work reorganization in the adult rat hippocampus. The Journal of Neuroscience, 17, 3727-3738.
Paxinos, G. and Watson, C. (1986) The rat brain in stereo-taxic coordinates. Academic, San Diego.
Ebendal, T. (1992) Function and evolution in the NG Ffamily and it sreceptors. Journal of Neuroscience Research, 32, 461-470.
Hefti, F., Knusel, B. and Lapchak, P.A. (1993) Protective effects of nerve growth factor and brain-derived neurotrophic factor on basal forebrain cholinergic neurons in adult rats with partial fimbrial transactions. Progress in Brain Research, 98, 257-263.
Backman, C., Rose, G.M., Hoffer, B.J., Henry, M.A., Bartus, R.T., Friden, P. and Granholm, A.C. (1996) Systemic administration of nerve growth factor conjugate reverses age-related cognitive dysfunction and prevents cholinergic neuron atrophy. The Journal of Neuroscience, 16, 5437-5442.
Isacson, O., Seo, H., Lin, L., Albeck, D. and Granholm, A.C. (2002) Alzheimer’s disease and Down’s syndrome: Roles of APP, tropic factors and Ach. Trends in Neurosciences, 25, 79-84.
Counts, S.E., Nadeem, M., Wuu, J., Ginsberg, S.D., Saragovi, H.U. and Mufson, E.J. (2004) Reduction of cortical Trk A but not p75 (NTR) protein in early-stage Alzheimer’s disease. Annals of Neurology, 56, 520-531. doi:10.1002/ana.20233
Lu, B. (2003) Pro-region of neurotrophins: Role in synaptic modulation. Neuron, 39, 735-738.
Suzuki, S., Numakawa, T., Shimazu, K., Koshimizu, H., Hara, T., Hatanaka, H., Mei, L., Liu, B. and Kojima, M. (2004) BDNF-induced recruitment of Trk B receptor into neuronal lipid rafts: Roles in synaptic modulation. The Journal of Cell Biology, 167, 1205-1215.
Smith, D.E., Robers, J., Gage, F.H. and Tusynski, M.H. (1999) Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proceedings of the National Academy Sciences of the United States of America, 96, 10893-10898.
Cotman, C.W. and Berchtold, N.C. (2002) Exercise: A behavioral intervention to enhance brain health and plasticity. Trends in Neurosciences, 25, 295-301.
Bibel, M. and Barde,Y.A. (2000) Neurotrophins: Key regulators of cell fate and cell shape in the vertebrate nervous system. Genes & Development, 14, 2919-2937.
Huang, E.J. and Reichardt, L.F. (2001) Neurotrophins: Roles in neuronal development and function. Annual Reviews of Neuroscience, 24, 677-736.
Chao, M.V. (2003) Neurotrophins and their receptors: A convergene point for many signaling pathways. Nature Reviews Neuroscience, 4, 299-309. doi:10.1038/nrn1078
Fischer, W., Wictorin, K., Bjorklund, A., Williams, L.R., Varon, S. and Gage, F.H. (1987) A melioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature, 329, 65-68.
Pizzo, D.P. and Thai, L.J. (2004) Intraparenchymal nerve growth factor improves behavioral deficits while mini- mizing the adverse effects of intracerebroventricular delivery. Neuroscience, 124, 743-755.
Jakubowska-Dogru, E. and Gumusbas, U. (2005) Chro- nic in-tracerebroventricular NGF administration improves working memory in young adult memory deficientrats. Neuroscience Letters, 382, 45-50.
Tuszynski, M.H., Thal, L., Pay, M., Salmon, D.P., Bakay, R., Patel, P., Blesch, A., Vahlsing, H.L., Ho, G., Tong, G., Potkin, S.G., Fallon, J., Hansen, L., Mufson, E.J., Kordower, J.H., Gall, C. and Conner, J. (2005) A phase I clinical trial of nerve growth factor gene therapy for Al- zheimer disease. Nature Medicine, 11, 551-555.
Conner, J.M., Lauterborn, J.C., Yan, Q., Gall, C.M. and Varon, S. (1997) Distribution of brain-derived neuro- trophic factor (BDNF) protein and mRNA in the normal adult CNS: Evident for anterograde axonal transport. The Journal of Neuroscience, 17, 2295-2313.
Tolwani, R.J., Buckmaster, P.S., Varma, S., Cosgaya, J.M., Wu, Y., Suri, C. and Shooter, E.M. (2002) BDNF overexpression increases dendrite complexity in hippo- campal dentate gyrus. Neuroscience, 114, 795-805.
Korte, M., Carroll, P., Wolf, E., Brem, G., Thoenen, H. and Bonhoeffer, T. (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proceedings of the National Academy Sciences of the United States of America, 92, 8856-8860.
Linnarsson, S., Bjorklund, A. and Ernfors, P. (1997) Learning deficits in BDNF mutant mice. European Jour- nal of Neuroscience, 9, 2518-2587.
Kuhn, H.G., Dickinson-Anson, H. and Gage, F.H. (1996) Neuro-genesis in thedentate gyrus of the adult ratage-related decrease of neuronal progenitor proliferation. The Journal of Neuroscience, 16, 2027-2033.
Kempermann, G., Kuhn, H.G. and Gage, F.H. (1997) More hip-pocampal neurons in adul tmice living in an enriched environment. Nature, 386, 493-495.
Gould, E., Beylin, A.,Tanapat, P., Reeves, A. and Shors, T.J. (1999) Learning enhances adult neurogenesis in the hippocam-pal formation. Nature Neuroscience, 2, 260- 265.
Van Praag, H., Kempermann, G. and Gage, F. (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neuroscience, 2, 266-270.
Gould, E., McEwen, B. S., Tanapat, P., Galea, L.A. and Fuchs, E. (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. The Journal of Neuroscience, 17, 2492-2498.
Gould, E., Tanapat, P., McEwen, B.S., Flugge, G. and Fuchs, E. (1998) Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proceedings of the National Academy Sciences of the United States of the America, 95, 3168-3171.
Tanapat, P., Galea, L.A. and Gould, E. (1998) Stress inhibits the proliferation of granule cell precursors in the developing dentate gyrus. International Journal of Developmental Neuroscience, 16, 235-239.
Fuchs, E., Flugge, G., McEwen, B.S., Tanapat, P., Gould, E. (1997) Chronicsubordination stress inhibits neuro- genesis and decreases the volume of the granule cell layer. Society Neurosci Abstr, 23, 317.
Kee, N., Sivalingam, S., Boonstra, R. and Wojtowicz, J.M. (2002) The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. Journal of Neuroscience Methods, 115, 97-105.