CELL PROLIFERATION CHANGES IN BRAIN SUBVENTRICULAR ZONE IN ADULT RATS AFTER в-AMYLOID PEPTIDE (25-35) ADMINISTRATION

Abstract

The effect of intracerebroventricular administration of the (25-35) fragment of amyloid-в peptide [Ав(25-35)] on cell proliferation in the subventricular zone of the hippocampal dentate gyrus was studied in adult rats. The animals were treated with either Ав(25-35) or Ав(35-25) at a dose of 15 nmol, control rats were injected with a vehicle (sterile water). 1-5 days after peptide administration, the animals were intraperitone-ally injected with a thymidine analogue 5-bromo-2'deoxyuridine (BrdU). Immunohistochemical detection of BrdU incorporation into DNA was performed on the frontal sections of the brains 6 and 12 days after treatment with peptides. 6 days after Ав peptide treatment, the total number of BrdU-positive cells in the subven-tricular zone was not significantly different in all groups studied. The total number of labelled cells was significantly decreased 12 days after surgery. However, in the Ав(25-35)-treated rats the number of BrdU-positive cells was higher as compared to that one in rats injected with control peptide or vehicle. Thus, intra-cerebroventricular administration of Ав(25-35) significantly increased cell proliferation in the subventricular zone.

Keywords

hippocampus / dentate gyrus / subventricular zone / cell proliferation

References

[1] Gage F.H. Neurogenesis in the adult brain. J. Neurosci., 2004, v. 22, № 3, p. 612-613.

[2] Gong Y., Chang L., Viola K.L. et al. Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc. Natl. Acad. Sci. USA, 2003, v. 100, № 18, p. 10417-10422.

[3] Haughey N.J., Liu D., Nath A. et al. Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. Neuromolecular Med., 2002, v. 1, № 2, p. 125-135.

[4] Haughey N.J., Nath A., Chan S.L. et al. Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease. J. Neurochem., 2002, v. 83, № 6, p. 1509-1524.

[5] Jin K., Galvan V., Xie L. et al. Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw,Ind) mice. Proc. Natl. Acad. Sci. USA, 2004, v. 101, № 36, p. 13363-13367.

[6] Jin K., Peel A.L., Mao X.O. et al. Increased hippocampal neurogenesis in Alzheimer's disease. Proc. Natl. Acad. Sci. USA, 2004, v. 101, № 1, p. 343-347.

[7] Lopez-Toledano M.A. and Shelanski M.L. Neurogenic effect of р-amyloid peptide in the development of neural stem cells. J. Neurosci., 2004, v. 24, № 23, p. 5439-5444.

[8] Nakagawa Y., Yuzuriha T. and Iwaki T. Active clearance of human amyloid р 1-42 peptide aggregates from the rat ventricular system. Neuropathology, 2004, v. 24, № 3, p. 194-200.

[9] Selkoe D.J. Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev., 2001, v. 81, № 2, p. 741-766.

[10] Stepanichev M.Yu., Onufriev M.V., Mitrokhina O.S. et al. Neurochemical, behavioral, and neuromorphological effects of central administration of beta-amyloid peptide (25-35) in rat. Нейрохимия, 2000, т. 17, № 4, с. 278-293.

[11] Stepanichev M.Yu., Zdobnova I.M., Zarubenko I.I. et al. Amyloid-beta (25-35)-induced memory impairments correlate with cell loss in rat hippocampus. Physiol. Behav., 2004, v. 80, № 5, p. 647-655.

RIGHTS & PERMISSIONS

Eco-Vector