Catalpol Upregulates Hippocampal GAP-43 Level of Aged Rats with Enhanced Spatial Memory and Behavior Response


Rehmannia glutinosa is a traditional Chinese medical herb and has a long history in cognitive deficits therapy. Its ther-apeutic efficacy has been confirmed by clinical studies. In this study, we attempted to investigate the effects of catalpol, an iridoid from Rehmannia glutinosa, on cognitive and behavioral function of aged rats with memory loss. 22 - 24 month Sprague-Dawley spontaneous rats of memory loss with aging were selected by step-down type passive avoidance test and randomly allocated to two groups: the aged rats with memory loss (control group) and the catal- pol-treated (5 mg/kg) group. We performed open-field and Y-maze test to evaluate special performance and behavior response before and after catalpol treatment for 5 and 10 days. Growth-associated protein (GAP-43) in hippocampus and frontal cortex was measured using immunohistochemistry and quantitative Western Blotting. The results showed that catalpol could significantly improve not only spatial learning and memory but also locomotor activity and ex-plora- tory behavior of aged rats with memory loss. GAP-43 protein in hippocampal CA3 region and dentate granule of catal- pol-treated rats was significantly enhanced than that of control group. Western blot analysis demonstrated a catal- pol-associated increase of GAP-43 in hippocampus of catalpol-treated rats and correlated with spatial memory, loco- motor activity and exploratory behavior. However, there was no difference in GAP-43 protein in frontal cortex between two groups. These results indicated that catalpol could enhance spatial performance and behavioral responses in aged rats with memory loss, and the mechanism may involve up-regulation of GAP-43 level of hippocampus in the brain. It also suggested that catalpol may be a useful natural drug for Alzheimer’s disease (AD) treatment by modulating hippo- campal neuroplasticity.

Share and Cite:

J. Liu, Y. Liu, W. Zou, L. Song and L. An, "Catalpol Upregulates Hippocampal GAP-43 Level of Aged Rats with Enhanced Spatial Memory and Behavior Response," Journal of Behavioral and Brain Science, Vol. 2 No. 4, 2012, pp. 495-504. doi: 10.4236/jbbs.2012.24058.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] W. C. Shyu, K. W. Li, H. F. Peng, et al., “Induction of GAP-43 Modulates Neuroplasticity in PBSC (CD34+) Implanted-Parkinson’s Model,” Journal of Neuroscience Research, Vol. 87, No. 9, 2009, pp. 2020-2033. doi:10.1002/jnr.22027
[2] J. Guevara, H. Dilhuydy, B. Espinosa, et al., “Coexistence of Reactive Plasticity and Neurodegeneration in Alzheimer Diseased Brains,” Histology and Histopathology, Vol. 19, No. 4, 2004, pp. 1075-1084.
[3] J. L. Rekart, K. Meiri and A. Routtenberg, “Hippocampal-Dependent Memory Is Impaired in Heterozygous GAP-43 Knockout Mice,” Hippocampus, Vol. 15, No. 1, 2005, pp. 1-7. doi:10.1002/hipo.20045
[4] D. Q. Li, Y. L. Duan, Y. M. Bao, C. P. Liu, Y. Liu and L. J. An, “Neuroprotection of Catalpol in Transient Global Ischemia in Gerbils,” Neuroscience Research, Vol. 50, No. 2, 2004, pp. 169-177. doi:10.1016/j.neures.2004.06.009
[5] B. Jiang, J. H. Liu, Y. M. Bao and L. J. An, “Catalpol Inhibits Apoptosis in Hydrogen Peroxide-induced PC12 Cells by Preventing Cytochrome c Release and Inactivating of Caspase Cascade,” Toxicon, Vol. 43, No. 1, 2004, pp. 53-59. doi:10.1016/j.toxicon.2003.10.017
[6] F. H. Gage, A. Bjorklund, V. Stenevi, S. B. Dunnett and P. A. Kelly, “Intrahippocampal Septal Grafts Ameliorate Learning Impairments in Aged Rats,” Science, Vol. 225, No. 4661, 1984, pp. 533-536. doi:10.1126/science.6539949
[7] K. Sidik and R. W. Morris, “Nonparametric Step-down Test Procedures for Finding Minimum Effective Dose,” Journal of Biopharmaceutical Statistics, Vol. 9, No. 2, 1999, pp. 217-240. doi:10.1081/BIP-100101173
[8] S. M. Brudzynski and S. Krol, “Analysis of Locomotor Activity in the Rat: Parallelism Index, a New Measure of Locomotor Exploratory Pattern,” Physiology & Behavior, Vol. 62, No. 3, 1997, pp. 635-642. doi:10.1016/S0031-9384(97)00189-3
[9] A. Routtenberg, “Measuring Memory in a Mouse Model of Alzheimer’s Disease,” Science, Vol. 277, No. 5327, 1997, pp. 839-840. doi:10.1126/science.277.5327.839
[10] J. Liu, Q. J. He, W. Zou, et al., “Catalpol Increases Hippocampal Neuroplasticity and Up-Regulates PKC and BDNF in the Aged Rats,” Brain Research, Vol. 1123, No. 1, 2006, pp. 68-79. doi:10.1016/j.brainres.2006.09.058
[11] A. A. OliveiraJr and H. M. Hodges, “Alzheimer’s Disease and Neural Transplantation as Prospective Cell Therapy,” Current Alzheimer Research, Vol. 2, No. 1, 2005, pp. 79- 95. doi:10.2174/1567205052772759
[12] H. Schmoll, S. Ramboiu, D. Platt, J. G. Herndon, C. Kessler and A. Popa-Wagner, “Age Influences the Expression of GAP-43 in the Rat Hippocampus Following Seizure,” Gerontology, Vol. 51, No. 4, 2005, pp. 215-224. doi:10.1159/000085117
[13] B. Teter and J. W. Ashford, “Neuroplasticity in Alzheimer’s Disease,” Journal of Neuroscience Research, Vol. 70, No. 3, 2002, pp. 402-437. doi:10.1002/jnr.10441
[14] G. W. Arendash, M. N. Gordon, M. Diamond, et al., “Behavioral Assessment of Alzheimer’s Transgenic Mice Followinglong-Term Aβ Vaccination: Task Specificity and Correlations between Aβ Deposition and Spatial Memory,” DNA and Cell Biology, Vol. 20, No. 11, 2001, pp. 737-744. doi:10.1089/10445490152717604
[15] H. Takatsu, K. Owada, K. Abe, M. Nakano and S. Urano, “Effect of Vitamin E on Learning and Memory Deficit in Aged Rats,” Journal of Nutritional Science and Vitaminology, Vol. 55, No. 5, 2009, pp. 389-393. doi:10.3177/jnsv.55.389
[16] Y. Cui, Z. Yan, S. Hou and Z. Chang, “Effect of Radix Rehmanniae Preparata on the Expression of c-Fos and NGF in Hippocampi and Learning and Memory in Rats with Damaged Thalamic Arcuate Nucleus,” Zhong Yao Cai, Vol. 27, No. 8, 2004, pp. 589-592.
[17] J. C. Hou, C. X. Zhang and S. L. Yang, “Effects of Dihuang Compound on Learning and Memory of Rats and Apoptosis of Hippocampal Cells in Alzheimer’s Disease,” Progress of Anatomical Sciences, Vol. 11, No. 2, 2005, pp. 111-113.
[18] Z. Wang, Q. Liu, R. Zhang, S. Liu, Z. Xia and Y. Hu, “Catalpol Ameliorates Beta Amyloid-induced Degeneraion of Cholinergic Neurons by Elevating Brain-Derived Neurotrophic Factors,” Neuroscience, Vol. 163, No. 4, 2009, pp. 1363-1372. doi:10.1016/j.neuroscience.2009.07.041
[19] D. Q. Li, Y. M. Bao, J. J. Zhao, C. P. Liu, Y. Liu and L. J. An, “Neuroprotective Properties of Catalpol in Transient Global Cerebral Ischemia in Gerbils: Dose-Response, Therapeutic Time-Window and Long-Term Efficacy,” Brain Research, Vol. 1029, No. 2, 2004, pp. 179-185. doi:10.1016/j.brainres.2004.09.041
[20] N. Traissard, K. Herbeaux, B. Cosquer, H. Jeltsch, B. Ferry, R. Galani, A. Pernon, M. Majchrzak and J. C. Cassel, “Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer’s Disease: Effects on Locomotor Activity and Memory Functions in Rats,” Neuropsychopharmacology, Vol. 32, No. 4, 2007, pp. 851-871. doi:10.1038/sj.npp.1301116
[21] N. Bogdanovic, P. Davidsson, I. Volkmann, B. Winblad and K. Blennow, “Growth-Associated Protein GAP-43 in the Frontal Cortex and in the Hippocampus in Alzheimer’s Disease: An Immunohistochemical and Quantitative Study,” Journal of Neural Transmission, Vol. 107, No. 4, 2000, pp. 463-478. doi:10.1007/s007020070088
[22] J. L. Rekart, M. M. Quinn, M. Mesulam and A. Routtenberg, “Subfield-Specific Increase in Brain Growth Protein in Postmortem Hippocampus of Alzheimer’s Patients,” Neuroscience, Vol. 126, No. 3, 2004, pp. 579-584. doi:10.1016/j.neuroscience.2004.03.060
[23] M. Sjogren, L. Minthon, P. Davidsson, et al., “CSF Levels of Tau, Beta-amyloid(1-42) and GAP-43 in Frontotemporal Dementia, Other Types of Dementia and Normal Aging,” Journal of Neural Transmission, Vol. 107, No. 5, 2000, pp. 563-579. doi:10.1007/s007020070079
[24] S. M. de la Monte, S. C. Ng and D. W. Hsu, “Aberrant GAP-43 Gene Expression in Alzheimer’s Disease,” American Journal of Pathology, Vol. 147, No. 4, 1995, pp. 934- 946.
[25] L. De Toledo-Morrell, M. P. Sullivan, F. Morrell, R. S. Wilson, D. A. Bennett and S. Spencer, “Alzheimer’s Disease: In Vivo Detection of Differential Vulnerability of Brain Regions,” Neurobiology of Aging, Vol. 18, No. 5, 1997, pp. 463-468. doi:10.1016/S0197-4580(97)00114-0
[26] T. Kadar, S. Dachir, B. Shukitt-Hale and A. Levy, “Subregional Hippocampal Vulnerability in Various Animal Models Leading to Cognitive Dysfunction,” Journal of Neural Transmission, Vol. 105, No. 8-9, 1998, pp. 987- 1004. doi:10.1007/s007020050107
[27] J. H. Morrison, “Hof PR: Selective Vulnerability of Corticocortical and Hippocampal Circuits in Aging and Alzheimer’s Disease,” Progress in Brain Research, Vol. 136, 2002, pp. 467-486. doi:10.1016/S0079-6123(02)36039-4
[28] M. R. Holahan, K. S. Honegger, N. Tabatadze and A. Routtenberg, “GAP-43 Dene Expression Regulates Information Storage,” Learning & Memory, Vol. 14, No. 6, 2007, pp. 407-415. doi:10.1101/lm.581907
[29] M. Yamazaki, K. Chiba and T. Mohri, “Neuritogenic Effect of Natural Iridoid Compounds on PC12 Cells and Its Possible Relation to Signaling Protein Kinases,” Biological & Pharmaceutical Bulletin, Vol. 19, No. 1996, pp. 791-795. doi:10.1248/bpb.19.791

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.