Skip to main content

Advertisement

SpringerLink
Log in

Altered expression of neurofilament 200 and amyloid-β peptide (1–40) in a rat model of chronic cerebral hypoperfusion

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Chronic cerebral hypoperfusion (CCH) is damaging to white matter in the brain. So far few studies have investigated long-term axonal damage following CCH. The aim of this study was to investigate the involvement of neurofilament 200 (NF200) and amyloid-β (1–40) [Aβ (1–40)] in the pathological mechanism for neuronal damage, and to quantify changes in their expression over time in a rat model of CCH. A rat model of CCH was established using partial bilateral ligation of the common carotid arteries. The extent of stenosis was verified by measuring the changes in cerebral blood flow after surgery. Histology was used to assess hippocampal neuronal pathology, and immunohistochemistry was used to quantify the expression of NF200 and Aβ (1–40) at 2, 4, and 12 weeks after surgery. The cerebral blood flow reduced to 33.89 ± 5.48 % at 2 weeks, 36.83 ± 4.63 % at 4 weeks and 51.44 ± 4.90 % at 12 weeks. Immunofluorescence staining of neuronal perikarya sections revealed a marked decrease in the population of surviving pyramidal cells in the hippocampal CA1 region, a significant up-regulation in the expression of Aβ (1–40), and a significant reduction in the expression of NF200 following CCH surgery. Moreover, this trend was increasingly obvious over time. Our data demonstrate that CCH leads to axonal damage over time. We also confirmed that the expression of Aβ (1–40) and NF200 may be useful biomarkers of axonal damage following CCH.

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

Similar content being viewed by others

References

  1. Bartzokis G (2004) Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease. Neurobiol Aging 25(1):5–18 (author reply 49–62)

    Article  CAS  PubMed  Google Scholar 

  2. Kanaan NM, Pigino GF, Brady ST et al (2013) Axonal degeneration in Alzheimer’s disease: when signaling abnormalities meet the axonal transport system. Exp Neurol 246:44–53

    Article  CAS  PubMed  Google Scholar 

  3. Sjögren M, Blomberg M, Jonsson M et al (2001) Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 66(3):510–516

    Article  PubMed  Google Scholar 

  4. Xiao AW, He J, Wang Q et al (2011) The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer’s disease. Neurosci Bull 27(5):287–299

    Article  CAS  PubMed  Google Scholar 

  5. Paik SK, Lee DS, Kim JY et al (2010) Quantitative ultrastructural analysis of the neurofilament 200-positive axons in the rat dental pulp. J Endod 36(10):1638–1642

    Article  PubMed  Google Scholar 

  6. Posmantur RM, Newcomb JK, Kampfl A et al (2000) Light and confocal microscopic studies of evolutionary changes in neurofilament proteins following cortical impact injury in the rat. Exp Neurol 161(1):15–26

    Article  CAS  PubMed  Google Scholar 

  7. Serbest G, Burkhardt MF, Siman R et al (2007) Temporal profiles of cytoskeletal protein loss following traumatic axonal injury in mice. Neurochem Res 32(12):2006–2014

    Article  CAS  PubMed  Google Scholar 

  8. Pigino G, Morfini G, Atagi Y et al (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. Proc Natl Acad Sci USA 106(14):5907–5912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shah SB, Nolan R, Davis E et al (2009) Examination of potential mechanisms of amyloid-induced defects in neuronal transport. Neurobiol Dis 36(1):11–25

    Article  CAS  PubMed  Google Scholar 

  10. Vagnoni A, Perkinton MS, Gray EH et al (2012) Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates Aβ production. Hum Mol Genet 21(13):2845–2854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. (1991) Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 325(7):445–453

  12. Ganzella M, de Oliveira ED, Comassetto DD et al (2012) Effects of chronic guanosine treatment on hippocampal damage and cognitive impairment of rats submitted to chronic cerebral hypoperfusion. Neurol Sci 33(5):985–997

    Article  PubMed  Google Scholar 

  13. Won JS, Kim J, Annamalai B et al (2013) Protective role of S-nitrosoglutathione (GSNO) against cognitive impairment in rat model of chronic cerebral hypoperfusion. J Alzheimers Dis 34(3):621–635

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Xu J, Wang Y, Li N et al (2012) L-3-n-butylphthalide improves cognitive deficits in rats with chronic cerebral ischemia. Neuropharmacology 62(7):2424–2429

    Article  CAS  PubMed  Google Scholar 

  15. Hainsworth AH, Markus HS (2008) Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab 28(12):1877–1891

    Article  PubMed  Google Scholar 

  16. Jiwa NS, Garrard P, Hainsworth AH (2010) Experimental models of vascular dementia and vascular cognitive impairment: a systematic review. J Neurochem 115(4):814–828

    Article  CAS  PubMed  Google Scholar 

  17. Sarti C, Pantoni L, Bartolini L et al (2002) Cognitive impairment and chronic cerebral hypoperfusion: what can be learned from experimental models. J Neurol Sci 203–204:263–266

    Article  PubMed  Google Scholar 

  18. Barros CA, Ekuni R, Moro MA et al (2009) The cognitive and histopathological effects of chronic 4-vessel occlusion in rats depend on the set of vessels occluded and the age of the animals. Behav Brain Res 197(2):378–387

    Article  PubMed  Google Scholar 

  19. Romanini CV, Schiavon AP, Ferreira ED et al (2010) Sildenafil prevents mortality and reduces hippocampal damage after permanent, stepwise, 4-vessel occlusion in rats. Brain Res Bull 81(6):631–640

    Article  CAS  PubMed  Google Scholar 

  20. Sekhon LH, Spence I, Morgan MK et al (1998) Long-term potentiation saturation in chronic cerebral hypoperfusion. J Clin Neurosci 5(3):323–328

    Article  CAS  PubMed  Google Scholar 

  21. Kaku Y, Yonekawa Y, Tsukahara T et al (1993) Alterations of a 200 kDa neurofilament in the rat hippocampus after forebrain ischemia. J Cereb Blood Flow Metab 13(3):402–408

    Article  CAS  PubMed  Google Scholar 

  22. Kriz J, Zhu Q, Julien JP et al (2000) Electrophysiological properties of axons in mice lacking neurofilament subunit genes: disparity between conduction velocity and axon diameter in absence of NF-H. Brain Res 885(1):32–44

    Article  CAS  PubMed  Google Scholar 

  23. Kitaguchi H, Tomimoto H, Ihara M et al (2009) Chronic cerebral hypoperfusion accelerates amyloid beta deposition in APPSwInd transgenic mice. Brain Res 1294:202–210

    Article  CAS  PubMed  Google Scholar 

  24. Liu H, Xing A, Wang X et al (2012) Regulation of β-amyloid level in the brain of rats with cerebrovascular hypoperfusion. Neurobiol Aging 33(4):826.e31–42

    Article  PubMed  Google Scholar 

  25. Decker H, Lo KY, Unger SM et al (2010) Amyloid-beta peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3beta in primary cultured hippocampal neurons. J Neurosci 30(27):9166–9171

    Article  CAS  PubMed  Google Scholar 

  26. Hiruma H, Katakura T, Takahashi S et al (2003) Glutamate and amyloid beta-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms. J Neurosci 23(26):8967–8977

    CAS  PubMed  Google Scholar 

  27. Rui Y, Tiwari P, Xie Z et al (2006) Acute impairment of mitochondrial trafficking by beta-amyloid peptides in hippocampal neurons. J Neurosci 26(41):10480–10487

    Article  CAS  PubMed  Google Scholar 

  28. Zempel H, Thies E, Mandelkow E et al (2010) Abeta oligomers cause localized Ca(2 +) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. J Neurosci 30(36):11938–11950

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Natural Science Foundation of China (Grant No.30170311).

Conflict of interest

There is no conflict of interest in this study.

Author information

Authors and Affiliations

  1. Department of Neurology, Xinqiao Hospital, The Third Military Medical University, No. 183 Xinqiao Street, Shapingba District, Chongqing, 400038, China

    Weihua Liang, Shifu Zhao, Qianning Li & Rongchuan Ceng

  2. No. 263 Hospital of Beijing Military Region, Beijing, 101149, China

    Weihua Liang

  3. General Hospital of Beijing PLA Military Region, Beijing, 100700, China

    Weiwei Zhang

  4. The 66083rd Army Unit of Beijing Military Area, Beijing, 102488, China

    Hua Liang

Authors
  1. Weihua Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiwei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shifu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qianning Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hua Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rongchuan Ceng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Weiwei Zhang or Shifu Zhao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liang, W., Zhang, W., Zhao, S. et al. Altered expression of neurofilament 200 and amyloid-β peptide (1–40) in a rat model of chronic cerebral hypoperfusion. Neurol Sci 36, 707–712 (2015). https://doi.org/10.1007/s10072-014-2014-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-014-2014-z

Keywords

Search

Navigation