Journal of Molecular Neuroscience

, Volume 41, Issue 1, pp 12–16 | Cite as

Microarray Profile of Brain Aging-Related Genes in the Frontal Cortex of SAMP8

  • Shao-Chun Chen
  • Gang Lu
  • Chu-Yan Chan
  • Yangchao Chen
  • Hua Wang
  • David Tai-Wai Yew
  • Zhong-Tang Feng
  • Hsiang-Fu Kung


This study examined the protein expression profile changes in the brain of senescence-accelerated mice/prone 8 (SAMP8) model. Two approaches, namely microarray and RT-PCR, were used in the study. Four genes, which are orthologous to human, were found to differentially express in the aging brain of mice. In this study, we examined the differentially expressed genes in the frontal cortex of the SAMP8 mice of two different ages (4 and 12 month old). Four orthologous genes (i.e., guanine nucleotide binding protein-alpha q polypeptide, kinesin family member 1B, sortilin 1, and somatostatin) showed significant changes in expression with aging. This study may provide important information on the mechanism of aging or aging-related diseases such as Alzheimer’s diseases.


Microarray Brain aging Orthologous gene SAMP8 RT-PCR 



This study was supported by the National Natural Science Foundation of P R China, grant number 30660050.

Supplementary material

12031_2009_9215_MOESM1_ESM.xls (28 kb)
Supplemental Table 1. Up-regulated genes with aging in the frontal cortex of SAMP8 (XLS 27 kb)
12031_2009_9215_MOESM2_ESM.xls (148 kb)
Supplemental Table 2. Down-regulated genes with aging in the frontal cortex of SAMP8 (XLS 148 kb)


  1. Adrio, F., Anadon, R., & Rodriguez-Moldes, I. (2008). Distribution of somatostatin immunoreactive neurons and fibres in the central nervous system of a chondrostean, the Siberian sturgeon (Acipenser baeri). Brain Research, 1209, 92–104.CrossRefPubMedGoogle Scholar
  2. Al-Shawi, R., Hafner, A., Olson, J., et al. (2008). Neurotoxic and neurotrophic roles of proNGF and the receptor sortilin in the adult and ageing nervous system. European Journal of Neuroscience, 27, 2103–2114.CrossRefPubMedGoogle Scholar
  3. Bohlen, P., Brazeau, P., Benoit, R., Ling, N., Esch, F., & Guillemin, R. (1980). Isolation and amino acid composition of two somatostatin-like peptides from ovine hypothalamus: somatostatin-28 and somatostatin-25. Biochemical and Biophysical Research Communications, 96, 725–734.CrossRefPubMedGoogle Scholar
  4. Chan, Y. C., Hosoda, K., Tsai, C. J., Yamamoto, S., & Wang, M. F. (2006). Favorable effects of tea on reducing the cognitive deficits and brain morphological changes in senescence-accelerated mice. Journal of Nutritional Science and Vitaminology (Tokyo), 52, 266–273.CrossRefGoogle Scholar
  5. Chen, H., Yao, W., Jin, D., et al. (2008). Cloning, expression pattern, chromosomal localization, and evolution analysis of porcine Gnaq, Gna11, and Gna14. Biochemical Genetics, 46, 398–405.CrossRefPubMedGoogle Scholar
  6. Cheng, X. R., Zhou, W. X., Zhang, Y. X., Zhou, D. S., Yang, R. F., & Chen, L. F. (2007). Differential gene expression profiles in the hippocampus of senescence-accelerated mouse. Neurobiology of Aging, 28, 497–506.CrossRefPubMedGoogle Scholar
  7. Conforti, L., Buckmaster, E. A., Tarlton, A., et al. (1999). The major brain isoform of kif1b lacks the putative mitochondria-binding domain. Mammalian Genome, 10, 617–622.CrossRefPubMedGoogle Scholar
  8. Conforti, L., Dell’Agnello, C., Calvaresi, N., et al. (2003). Kif1Bbeta isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis. Journal of Neuroscience Research, 71, 732–739.CrossRefPubMedGoogle Scholar
  9. Dong, Q., Shenker, A., Way, J., et al. (1995). Molecular cloning of human G alpha q cDNA and chromosomal localization of the G alpha q gene (GNAQ) and a processed pseudogene. Genomics, 30, 470–475.CrossRefPubMedGoogle Scholar
  10. Esquifino, A. I., Cano, P., Jimenez, V., Reyes Toso, C. F., & Cardinali, D. P. (2004). Changes of prolactin regulatory mechanisms in aging: 24-h rhythms of serum prolactin and median eminence and adenohypophysial concentration of dopamine, serotonin, (gamma-aminobutyric acid, taurine and somatostatin) in young and aged rats. Experimental Gerontology, 39, 45–52.CrossRefPubMedGoogle Scholar
  11. Foster, T. C. (2005). Interaction of rapid signal transduction cascades and gene expression in mediating estrogen effects on memory over the life span. Frontiers in Neuroendocrinology, 26, 51–64.CrossRefPubMedGoogle Scholar
  12. Getchell, T. V., Peng, X., Green, C. P., et al. (2004). In silico analysis of gene expression profiles in the olfactory mucosae of aging senescence-accelerated mice. Journal of Neuroscience Research, 77, 430–452.CrossRefPubMedGoogle Scholar
  13. Gong, T. W., Winnicki, R. S., Kohrman, D. C., & Lomax, M. I. (1999). A novel mouse kinesin of the UNC-104/KIF1 subfamily encoded by the Kif1b gene. Gene, 239, 117–127.CrossRefPubMedGoogle Scholar
  14. Hermey, G., Keat, S. J., Madsen, P., Jacobsen, C., Petersen, C. M., & Gliemann, J. (2003). Characterization of sorCS1, an alternatively spliced receptor with completely different cytoplasmic domains that mediate different trafficking in cells. Journal of Biological Chemistry, 278, 7390–7396.CrossRefPubMedGoogle Scholar
  15. Jacobsen, L., Madsen, P., Jacobsen, C., Nielsen, M. S., Gliemann, J., & Petersen, C. M. (2001). Activation and functional characterization of the mosaic receptor SorLA/LR11. Journal of Biological Chemistry, 276, 22788–22796.CrossRefPubMedGoogle Scholar
  16. Jansen, P., Giehl, K., Nyengaard, JR., et al. (2007). Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury. Nature Neuroscience, 10(11), 1449–1457.CrossRefPubMedGoogle Scholar
  17. Kirkwood, T. B. (2008). A systematic look at an old problem. Nature, 451, 644–647.CrossRefPubMedGoogle Scholar
  18. Kumar, V. B., Farr, S. A., Flood, J. F., et al. (2000). Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice. Peptides, 21, 1769–1775.CrossRefPubMedGoogle Scholar
  19. Lu, T., Pan, Y., Kao, S. Y., et al. (2004). Gene regulation and DNA damage in the ageing human brain. Nature, 429, 883–891.CrossRefPubMedGoogle Scholar
  20. Mazella, J., Zsurger, N., Navarro, V., et al. (1998). The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. Journal of Biological Chemistry, 273, 26273–26276.CrossRefPubMedGoogle Scholar
  21. Munck Petersen, C., Nielsen, M. S., Jacobsen, C., et al. (1999). Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding. EMBO Journal, 18, 595–604.CrossRefPubMedGoogle Scholar
  22. Nabeshi, H., Oikawa, S., Inoue, S., Nishino, K., & Kawanishi, S. (2006). Proteomic analysis for protein carbonyl as an indicator of oxidative damage in senescence-accelerated mice. Free Radical Research, 40, 1173–1181.CrossRefPubMedGoogle Scholar
  23. Nangaku, M., Sato-Yoshitake, R., Okada, Y., et al. (1994). KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell, 79, 1209–1220.CrossRefPubMedGoogle Scholar
  24. Nonaka, N., Banks, W. A., Mizushima, H., Shioda, S., & Morley, J. E. (2002). Regional differences in PACAP transport across the blood-brain barrier in mice: a possible influence of strain, amyloid beta protein, and age. Peptides, 23, 2197–2202.CrossRefPubMedGoogle Scholar
  25. Nykjaer, A., Lee, R., Teng, K. K., et al. (2004). Sortilin is essential for proNGF-induced neuronal cell death. Nature, 427, 843–848.CrossRefPubMedGoogle Scholar
  26. Pantelidou, M., Zographos, S. E., Lederer, C. W., Kyriakides, T., Pfaffl, M. W., & Santama, N. (2007). Differential expression of molecular motors in the motor cortex of sporadic ALS. Neurobiology of Disease, 26, 577–589.CrossRefPubMedGoogle Scholar
  27. Patel, Y. C. (1999). Somatostatin and its receptor family. Frontiers in Neuroendocrinology, 20, 157–198.CrossRefPubMedGoogle Scholar
  28. Patzelt, C., Neilsen, D., Carroll, R., et al. (1980). Studies on the biosynthesis of the other peptide hormones of the rat islets of Langerhans. Biochemical Society Transactions, 8, 411–413.PubMedGoogle Scholar
  29. Poon, H. F., Joshi, G., Sultana, R., et al. (2004). Antisense directed at the Abeta region of APP decreases brain oxidative markers in aged senescence accelerated mice. Brain Research, 1018, 86–96.CrossRefPubMedGoogle Scholar
  30. Poon, H. F., Farr, S. A., Banks, W. A., et al. (2005). Proteomic identification of less oxidized brain proteins in aged senescence-accelerated mice following administration of antisense oligonucleotide directed at the Abeta region of amyloid precursor protein. Brain Res Mol Brain Res, 138, 8–16.CrossRefPubMedGoogle Scholar
  31. Reichlin, S. (1983). Somatostatin. New England Journal of Medicine, 309, 1495–1501.PubMedCrossRefGoogle Scholar
  32. Rodriguez, M. I., Escames, G., Lopez, L. C., et al. (2007). Chronic melatonin treatment reduces the age-dependent inflammatory process in senescence-accelerated mice. Journal of Pineal Research, 42, 272–279.CrossRefPubMedGoogle Scholar
  33. Sandberg, R., Yasuda, R., Pankratz, D. G., et al. (2000). Regional and strain-specific gene expression mapping in the adult mouse brain. Proceedings of the National Academy of Sciences of the United States of America, 97, 11038–11043.CrossRefPubMedGoogle Scholar
  34. Scheiderer, C. L., Smith, C. C., McCutchen, E., et al. (2008). Coactivation of M(1) muscarinic and alpha1 adrenergic receptors stimulates extracellular signal-regulated protein kinase and induces long-term depression at CA3-CA1 synapses in rat hippocampus. Journal of Neuroscience, 28, 5350–5358.CrossRefPubMedGoogle Scholar
  35. Schindler, M., Humphrey, P. P., & Emson, P. C. (1996). Somatostatin receptors in the central nervous system. Progress in Neurobiology, 50, 9–47.CrossRefPubMedGoogle Scholar
  36. Sureda, F. X., Gutierrez-Cuesta, J., Romeu, M., et al. (2006). Changes in oxidative stress parameters and neurodegeneration markers in the brain of the senescence-accelerated mice SAMP-8. Experimental Gerontology, 41, 360–367.CrossRefPubMedGoogle Scholar
  37. Tajes, M., Gutierrez-Cuesta, J., Folch, J., et al. (2008). Lithium treatment decreases activities of tau kinases in a murine model of senescence. Journal of Neuropathology and Experimental Neurology, 67, 612–623.CrossRefPubMedGoogle Scholar
  38. Takeda, T., Hosokawa, M., Takeshita, S., et al. (1981). A new murine model of accelerated senescence. Mechanism of Ageing and Development, 17, 183–194.CrossRefGoogle Scholar
  39. Takemura, R., Nakata, T., Okada, Y., Yamazaki, H., Zhang, Z., & Hirokawa, N. (1996). mRNA expression of KIF1A, KIF1B, KIF2, KIF3A, KIF3B, KIF4, KIF5, and cytoplasmic dynein during axonal regeneration. Journal of Neuroscience, 16, 31–35.PubMedGoogle Scholar
  40. Terry, R. D. (2006). Alzheimer’s disease and the aging brain. Journal of Geriatric Psychiatry and Neurology, 19, 125–128.CrossRefPubMedGoogle Scholar
  41. Tostivint, H., Joly, L., Lihrmann, I., Ekker, M., & Vaudry, H. (2004). Chromosomal localization of three somatostatin genes in zebrafish. Evidence that the [Pro2]-somatostatin-14 isoform and cortistatin are encoded by orthologous genes. Journal of Molecular Endocrinology, 33, R1–R8.CrossRefPubMedGoogle Scholar
  42. Wang, Z. P., Man, S. Y., & Tang, F. (1993). Age-related changes in the contents of neuropeptides in the rat brain and pituitary. Neurobiology of Aging, 14, 529–534.CrossRefPubMedGoogle Scholar
  43. Wei, X., Zhang, Y., & Zhou, J. (1999). Alzheimer’s disease-related gene expression in the brain of senescence accelerated mouse. Neuroscience Letters, 268, 139–142.CrossRefPubMedGoogle Scholar
  44. Wu, Y., Zhang, A. Q., & Yew, D. T. (2005). Age related changes of various markers of astrocytes in senescence-accelerated mice hippocampus. Neurochemistry International, 46, 565–574.CrossRefPubMedGoogle Scholar
  45. Xu, J., Shi, C., Li, Q., Wu, J., Forster, E. L., & Yew, D. T. (2007). Mitochondrial dysfunction in platelets and hippocampi of senescence-accelerated mice. Journal of Bioenergetics and Biomembranes, 39, 195–202.CrossRefPubMedGoogle Scholar
  46. Zhang, G. R., Cheng, X. R., Zhou, W. X., & Zhang, Y. X. (2008). Age-related expression of STUB1 in senescence-accelerated mice and its response to anti-Alzheimer’s disease traditional Chinese medicine. Neuroscience Letters, 438, 371–375.CrossRefPubMedGoogle Scholar
  47. Zhang, G. R., Cheng, X. R., Zhou, W. X., & Zhang, Y. X. (2009). Age-related expression of calcium/calmodulin-dependent protein kinase II A in the hippocampus and cerebral cortex of senescence accelerated mouse prone/8 mice is modulated by anti-Alzheimer’s disease drugs. Neuroscience, 159, 308–315.CrossRefPubMedGoogle Scholar
  48. Zhao, C., Takita, J., Tanaka, Y., et al. (2001). Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell, 105, 587–597.CrossRefPubMedGoogle Scholar
  49. Zheng, Y., Cheng, X. R., Zhou, W. X., & Zhang, Y. X. (2008). Gene expression patterns of hippocampus and cerebral cortex of senescence-accelerated mouse treated with Huang-Lian-Jie-Du decoction. Neuroscience Letters, 439, 119–124.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press 2009

Authors and Affiliations

  • Shao-Chun Chen
    • 1
    • 3
  • Gang Lu
    • 4
  • Chu-Yan Chan
    • 3
  • Yangchao Chen
    • 3
  • Hua Wang
    • 3
  • David Tai-Wai Yew
    • 5
  • Zhong-Tang Feng
    • 2
  • Hsiang-Fu Kung
    • 3
  1. 1.Department of AnatomyKunming Medical CollegeKunmingPeople’s Republic of China
  2. 2.Institute of NeuroscienceKunming Medical CollegeKunmingPeople’s Republic of China
  3. 3.Stanley Ho Centre for Emerging Infectious DiseasesThe Chinese University of Hong KongShatinPeople’s Republic of China
  4. 4.Department of SurgeryThe Chinese University of Hong KongShatinPeople’s Republic of China
  5. 5.Department of Anatomy, Faculty of MedicineThe Chinese University of Hong KongShatinPeople’s Republic of China

Personalised recommendations