Skip to main content
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2010 Feb 3;26(1):37–46. doi: 10.1007/s12264-010-6122-3

Expression of the apoptosis-related proteins caspase-3 and NF-κB in the hippocampus of Tg2576 mice

凋亡相关基因caspase-3 和NF-κB 在阿尔茨海默病Tg2576 转基因小鼠海马内的表达

Yan-Li Niu 1, Wei-Juan Zhang 1, Ping Wu 1, Bin Liu 1, Guo-Tao Sun 1, Dong-Ming Yu 1, Jin-Bo Deng 1,
PMCID: PMC5560375  PMID: 20101271

Abstract

Objective

To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease (AD), especially the role of NF-κB in the regulation of neuroapoptosis.

Methods

Caspase-3 and NF-κB (p50) expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0–180, using Nissl staining, immunohistochemistry and RT-PCR methods.

Results

Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF-κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 (P < 0.01 or P < 0.05). Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB.

Conclusion

The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.

Keywords: Alzheimer’s disease, Tg2576 transgenic mice, caspase-3, hippocampus, apoptosis, NF-κB

Footnotes

These authors contributed equally to this work.

References

  • [1].Wang X.P., Ding H.L. Alzheimer’s disease: epidemiology, genetics, and beyond. Neurosci Bull. 2008;24:105–109. doi: 10.1007/s12264-008-0105-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2].Hsiao K., Chapman P., Nilsen S., Eckman C., Harigaya Y., Younkin S., et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in TM. Science. 1996;274:99–102. doi: 10.1126/science.274.5284.99. [DOI] [PubMed] [Google Scholar]
  • [3].Rohrer M.S., Lazio M.P., Seifert H.S. A real-time semi-quantitative RT-PCR assay demonstrates that the pilE sequence dictates the frequency and characteristics of pilin antigenic variation in Neisseria gonorrhoeae. Nucleic Acids Res. 2005;33:3363–3371. doi: 10.1093/nar/gki650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Kawai T., Akira S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med. 2007;13:460–469. doi: 10.1016/j.molmed.2007.09.002. [DOI] [PubMed] [Google Scholar]
  • [5].Lossi L., Merighi A. In vivo cellular and molecular mechanisms of neuronal apoptosis in the mammalian CNS. Prog Neurobiol. 2003;69:287–312. doi: 10.1016/S0301-0082(03)00051-0. [DOI] [PubMed] [Google Scholar]
  • [6].Buss R.R., Sun W., Oppenheim R.W. Adaptive roles of programmed cell death during nervous system development. Annu Rev Neurosci. 2006;29:1–35. doi: 10.1146/annurev.neuro.29.051605.112800. [DOI] [PubMed] [Google Scholar]
  • [7].Ohsawa S., Miura M. Programmed cell death in the nervous system. Brain Nerve. 2008;60:343–350. [PubMed] [Google Scholar]
  • [8].Bouras C., Hof P.R., Giannakopoulos P., Michel J.-P., Morrison J.H. Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: A quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb Cortex. 1994;4:138–150. doi: 10.1093/cercor/4.2.138. [DOI] [PubMed] [Google Scholar]
  • [9].Rohn T.T., Head E., Su J.H., Anderson A.J., Bahr B.A., Cotman C.W., et al. Correlation between caspase activation and neurofibrillary tangle formation in Alzheimer’s disease. Am J Pathol. 2001;158:189–198. doi: 10.1016/S0002-9440(10)63957-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Kril J.J., Patel S., Harding A.J., Halliday G.M. Neuron loss from the hippocampus of Alzheimer’s disease exceeds extracellular neurofibrillary tangle formation. Acta Neuropathol. 2002;103:370–376. doi: 10.1007/s00401-001-0477-5. [DOI] [PubMed] [Google Scholar]
  • [11].Wenk G.L. Neuropathologic changes in Alzheimer’s disease. J Clini Psychiatry. 2003;64(Suppl9):7–10. [PubMed] [Google Scholar]
  • [12].Hansen L.A., DeTeresa R., Davies P., Terry R.D. Neocortical morphometry, lesion counts, and choline acetyltransferase levels in the age spectrum of Alzheimer’s disease. Neurology. 1988;38:48–54. doi: 10.1212/wnl.38.1.48. [DOI] [PubMed] [Google Scholar]
  • [13].Schmitz C., Rutten B.P., Pielen A., Schäfer S., Wirths O., Tremp G., et al. Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer’s disease. Am J Pathol. 2004;164:1495–1502. doi: 10.1016/S0002-9440(10)63235-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Su J.H., Anderson A.J., Cummings B.J., Cotman C.W. Immunohistochemical evidence for apoptosis in Alzheimer’s disease. Neuroreport. 1994;5:2529–2533. doi: 10.1097/00001756-199412000-00031. [DOI] [PubMed] [Google Scholar]
  • [15].Lossi L., Gambino G. Apoptosis of the cerebellar neurons. Histol Histopathol. 2008;23:367–380. doi: 10.14670/HH-23.367. [DOI] [PubMed] [Google Scholar]
  • [16].Jiang Q., Hu Y., Wu P., Cheng X., Li M., Yu D., et al. Prenatal alcohol exposure and the neuroapoptosis with long-term effect in visual cortex of mice. Alcohol Alcohol. 2007;42:285–290. doi: 10.1093/alcalc/agm032. [DOI] [PubMed] [Google Scholar]
  • [17].McDonald P.P., Bald A., Cassatella M.A. Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils. Blood. 1997;89:3421–3433. [PubMed] [Google Scholar]
  • [18].Lind M.H., Rozell B., Wallin R.P.A., van Hogerlinden M., Ljunggren H.G., Toftgard R., et al. Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition. Proc Natl Acad Sci U S A. 2004;101:4972–4977. doi: 10.1073/pnas.0307106101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Yang L., Tao L.Y., Chen X.P. Roles of NF-κB in central nervous system damage and repair. Neurosci Bull. 2007;23:307–313. doi: 10.1007/s12264-007-0046-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Van Antwerp D.J., Martin S.J., Verma I.M., Green D.R. Inhibition of TNF-induced apoptosis by NF-kappa B. Trends Cell Biol. 1998;8:107–111. doi: 10.1016/S0962-8924(97)01215-4. [DOI] [PubMed] [Google Scholar]
  • [21].Aranha M.M., Borralho P.M., Ravasco P., Moreira da Silva I.B., Correia L., Fernandes A., et al. NF-kappaB and apoptosis in colorectal tumourigenesis. Eur J Clin Invest. 2007;37:416–424. doi: 10.1111/j.1365-2362.2007.01801.x. [DOI] [PubMed] [Google Scholar]
  • [22].Chung W.H., Boo S.H., Chung M.K., Lee H.S., Cho Y.S., Hong S.H. Proapoptotic effects of NF-kappaB on cisplatin-induced cell death in auditory cell line. Acta Otolaryngol. 2008;128:1063–1070. doi: 10.1080/00016480701881811. [DOI] [PubMed] [Google Scholar]
  • [23].Friedlander R.M. Apoptosis and caspases in neurodegenerative diseases. N Engl J Med. 2003;348:1365–1375. doi: 10.1056/NEJMra022366. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES