Skip to main content
SpringerLink
Log in

The Hippocampal Proteomic Analysis of Senescence-Accelerated Mouse: Implications of Uchl3 and Mitofilin in Cognitive Disorder and Mitochondria Dysfunction in SAMP8

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Senescence-accelerated mouse prone 8 (SAMP8) is considered as a useful animal model for age-related learning and memory impairments. Hippocampus, a critical brain region associated with cognitive decline during normal aging and various neurodegenerative diseases, appeared a series of abnormalities in SAMP8. To investigate the molecular mechanisms underlying age-related cognitive disorders, we used 2-DE coupled with MALDI TOF/TOF MS to analyze the differential protein expression of the hippocampus of SAMP8 at 6-month-old compared with the age-matched SAM/resistant 1 (SAMR1) which shows normal aging process. Two proteins were found to be markedly changed in SAMP8 as compared to SAMR1: ubiquitin carboxyl-terminal hydrolase L3 (Uchl3), implicating in cytosolic proteolysis of oxidatively damaged proteins, was down-regulated while mitofilin, a vital protein for normal mitochondria function, exhibited four isoforms with a consistent basic shift of isoelectric point among the soluble hippocampal proteins in SAMP8 compared with SAMR1. The alterations were confirmed by Western blotting analysis. The analysis of their expression changes may shed light on the mechanisms of learning and memory deficits and mitochondrial dysfunction as observed in SAMP8.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig.3 
Fig. 4

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

CHAPS:

3-(3-(Cholamidopropyl) dimethylammonio) propanesulfonate

DTT:

Dithiothreitol

MALDI TOF/TOF:

Matrix-assisted laser desorption ionization time-of-flight/time-of-flight

MS:

Mass spectrometry

ROS:

Reactive oxygen species

SOD1:

Cu, Zn-superoxide dismutase

SOD2:

Manganese superoxide dismutase

SAMP8:

Senescence-accelerated mouse prone 8

Uchl3:

Ubiquitin carboxyl-terminal hydrolase L3

PMF:

Peptide mapping fingerprinting

2-DE:

Two dimensional electrophoresis

References

  1. Takeda T, Hosokawa M, Takeshita S et al (1981) A new murine model of accelerated senescence. Mech Ageing Dev 17(2):183–194

    Article  PubMed  CAS  Google Scholar 

  2. Flood JF, Morley JE (1998) Learning and memory in the SAMP8 mouse. Neurosci Biobehav Rev 22(1):1–20

    Article  PubMed  CAS  Google Scholar 

  3. Sureda FX, 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. Exp Gerontol 41(4):360–367

    Article  PubMed  CAS  Google Scholar 

  4. Tanaka J, Okuma Y, Tomobe K et al (2005) The age-related degeneration of oligodendrocytes in the hippocampus of the senescence-accelerated mouse (SAM) P8: a quantitative immunohistochemical study. Biol Pharm Bull 28(4):615–618

    Article  PubMed  CAS  Google Scholar 

  5. Wu Y, Zhang AQ, Yew DT (2005) Age related changes of various markers of astrocytes in senescence-accelerated mice hippocampus. Neurochem Int 46(7):565–574

    Article  PubMed  CAS  Google Scholar 

  6. Wei X, Zhang Y, Zhou J (1999) Alzheimer’s disease-related gene expression in the brain of senescence accelerated mouse. Neurosci Lett 268(3):139–142

    Article  PubMed  CAS  Google Scholar 

  7. Morley JE, Kumar VB, Bernardo AE et al (2000) Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory. Peptides 21(12):1761–1767

    Article  PubMed  CAS  Google Scholar 

  8. Cheng XR, Zhou WX, Zhang YX et al (2007) Differential gene expression profiles in the hippocampus of senescence-accelerated mouse. Neurobiol Aging 28(4):497–506

    Article  PubMed  CAS  Google Scholar 

  9. Butterfield DA, Poon HF (2005) The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer’s disease. Exp Gerontol 40(10):774–783

    Article  PubMed  CAS  Google Scholar 

  10. Tomobe K, Okuma Y, Nomura Y (2007) Impairment of CREB phosphorylation in the hippocampal CA1 region of the senescence-accelerated mouse (SAM) P8. Brain Res 1141:214–217

    Article  PubMed  CAS  Google Scholar 

  11. Okuma Y, Nomura Y (1998) Senescence-accelerated mouse (SAM) as an animal model of senile dementia: pharmacological, neurochemical and molecular biological approach. Jpn J Pharmacol 78(4):399–404

    Article  PubMed  CAS  Google Scholar 

  12. Kurokawa T, Asada S, Nishitani S et al (2001) Age-related changes in manganese superoxide dismutase activity in the cerebral cortex of senescence-accelerated prone and resistant mouse. Neurosci Lett 298(2):135–138

    Article  PubMed  CAS  Google Scholar 

  13. Fujibayashi Y, Yamamoto S, Waki A et al (1998) Increased mitochondrial DNA deletion in the brain of SAMP8, a mouse model for spontaneous oxidative stress brain. Neurosci Lett 254(2):109–112

    Article  PubMed  CAS  Google Scholar 

  14. Xu J, Shi C, Li Q et al (2007) Mitochondrial dysfunction in platelets and hippocampi of senescence-accelerated mice. J Bioenerg Biomembr 39(2):195–202

    Article  PubMed  CAS  Google Scholar 

  15. Alvarez-Garcia O, Vega-Naredo I, Sierra V et al (2006) Elevated oxidative stress in the brain of senescence-accelerated mice at 5 months of age. Biogerontology 7(1):43–52

    Article  PubMed  CAS  Google Scholar 

  16. Colas D, Gharib A, Bezin L et al (2006) Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain. BMC Neurosci 7:81

    Article  PubMed  Google Scholar 

  17. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247

    Article  PubMed  CAS  Google Scholar 

  18. Nabeshi H, Oikawa S, Inoue S et al (2006) Proteomic analysis for protein carbonyl as an indicator of oxidative damage in senescence-accelerated mice. Free Radic Res 40(11):1173–1181

    Article  PubMed  CAS  Google Scholar 

  19. Poon HF, Castegna A, Farr SA et al (2004) Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain. Neuroscience 126(4):915–926

    Article  PubMed  CAS  Google Scholar 

  20. Hegde AN, Inokuchi K, Pei W et al (1997) Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia. Cell 89(1):115–126

    Article  PubMed  CAS  Google Scholar 

  21. Wood MA, Kaplan MP, Brensinger CM et al (2005) Ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory. Hippocampus 15(5):610–621

    Article  PubMed  CAS  Google Scholar 

  22. Barrachina M, Castano E, Dalfo E et al (2006) Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies. Neurobiol Dis 22(2):265–273

    Article  PubMed  CAS  Google Scholar 

  23. Armbrecht HJ, Boltz MA, Kumar VB et al (1999) Effect of age on calcium-dependent proteins in hippocampus of senescence-accelerated mice. Brain Res 842(2):287–293

    Article  PubMed  CAS  Google Scholar 

  24. Yang W, Liu P, Liu Y et al (2006) Proteomic analysis of rat pheochromocytoma PC12 cells. Proteomics 6(10):2982–2990

    Article  PubMed  CAS  Google Scholar 

  25. Candiano G, Bruschi M, Musante L et al (2004) Blue silver: a very sensitive colloidal Coomassie G-250 staining for proteome analysis. Electrophoresis 25(9):1327–1333

    Article  PubMed  CAS  Google Scholar 

  26. Larsen CN, Price JS, Wilkinson KD (1996) Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues. Biochemistry 35(21):6735–6744

    Article  PubMed  CAS  Google Scholar 

  27. Larsen CN, Krantz BA, Wilkinson KD (1998) Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry 37(10):3358–3368

    Article  PubMed  CAS  Google Scholar 

  28. Hershko A, Ciechanover A, Varshavsky A (2000) Basic Medical Research Award. The ubiquitin system. Nat Med 6(10):1073–1081

    Article  PubMed  CAS  Google Scholar 

  29. DiAntonio A, Haghighi AP, Portman SL et al (2001) Ubiquitination-dependent mechanisms regulate synaptic growth and function. Nature 412(6845):449–452

    Article  PubMed  CAS  Google Scholar 

  30. Gieffers C, Korioth F, Heimann P et al (1997) Mitofilin is a transmembrane protein of the inner mitochondrial membrane expressed as two isoforms. Exp Cell Res 232(2):395–399

    Article  PubMed  CAS  Google Scholar 

  31. Myung JK, Gulesserian T, Fountoulakis M et al (2003) Deranged hypothetical proteins Rik protein, Nit protein 2 and mitochondrial inner membrane protein, Mitofilin, in fetal Down syndrome brain. Cell Mol Biol (Noisy-le-grand) 49(5):739–746

    CAS  Google Scholar 

  32. Wishart TM, Paterson JM, Short DM et al (2007) Differential proteomics analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene. Mol Cell Proteomics 6(8):1318–1330

    Article  PubMed  CAS  Google Scholar 

  33. Johnston SC, Larsen CN, Cook WJ et al (1997) Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. Embo J 16(13):3787–3796

    Article  PubMed  CAS  Google Scholar 

  34. Nishikawa T, Takahashi JA, Fujibayashi Y et al (1998) An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model. Neurosci Lett 254(2):69–72

    Article  PubMed  CAS  Google Scholar 

  35. Omori A, Ichinose S, Kitajima S et al (2002) Gerbils of a seizure-sensitive strain have a mitochondrial inner membrane protein with different isoelectric points from those of a seizure-resistant strain. Electrophoresis 23(24):4167–4174

    Article  PubMed  CAS  Google Scholar 

  36. Lai Y, Chen Y, Watkins SC et al (2007) Identification of poly-ADP-ribosylated mitochondrial proteins after traumatic brain injury. J Neurochem

Download references

Acknowledgements

This work was supported by grants from National Basic Research Program of China (No. 2006CB910103).

Author information

Authors and Affiliations

  1. The National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, 100871, P.R. China

    Qingsong Wang, Yashu Liu, Xiao Zou, Qian Wang, Mingrui An, Xin Guan, Jintang He, Yuanpeng Tong & Jianguo Ji

Authors
  1. Qingsong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yashu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mingrui An
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xin Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jintang He
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuanpeng Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jianguo Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianguo Ji.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, Q., Liu, Y., Zou, X. et al. The Hippocampal Proteomic Analysis of Senescence-Accelerated Mouse: Implications of Uchl3 and Mitofilin in Cognitive Disorder and Mitochondria Dysfunction in SAMP8. Neurochem Res 33, 1776–1782 (2008). https://doi.org/10.1007/s11064-008-9628-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-008-9628-6

Keywords

Search

Navigation