QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 1, 2003, 23(26):8967-8977

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Hiruma, H. Articles by Kawakami, T. Search for Related Content PubMed PubMed Citation Articles by Hiruma, H. Articles by Kawakami, T.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Glutamate and Amyloid -Protein Rapidly Inhibit Fast Axonal Transport in Cultured Rat Hippocampal Neurons by Different Mechanisms

Hiromi Hiruma,¹ Takashi Katakura,¹ Sanae Takahashi,¹ Takafumi Ichikawa,² and Tadashi Kawakami¹

Departments of ¹Physiology and ²Biochemistry, Kitasato University School of Medicine, Sagamihara 228-8555, Japan

Impairment of axonal transport leads to neurodegeneration and synapse loss. Glutamate and amyloid -protein (A) have critical roles in the pathogenesis of Alzheimer's disease (AD). Here we show that both agents rapidly inhibit fast axonal transport in cultured rat hippocampal neurons. The effect of glutamate (100 µM), but not of A_25-35 (20 µM), was reversible, was mimicked by NMDA or AMPA, and was blocked by NMDA and AMPA antagonists and by removal of extracellular Ca²⁺. The effect of A_25-35 was progressive and irreversible, was prevented by the actin-depolymerizing agent latrunculin B, and was mimicked by the actin-polymerizing agent jasplakinolide. A_25-35 induced intracellular actin aggregation, which was prevented by latrunculin B. A_31-35 but not A_15-20 exerted effects similar to those of A_25-35. Full-length A_1-42 incubated for 7 d, which specifically contained 30-100 kDa molecular weight assemblies, also caused an inhibition of axonal transport associated with intracellular actin aggregation, whereas freshly dissolved A_1-40, incubated A_1-40, and fresh A_1-42 had no effect. These results suggest that glutamate inhibits axonal transport via activation of NMDA and AMPA receptors and Ca²⁺ influx, whereas A exerts its inhibitory effect via actin polymerization and aggregation. The ability of A to inhibit axonal transport seems to require active amino acid residues, which is probably present in the 31-35 sequence. Full-length A may be effective when it represents a structure in which these active residues can access the cell membrane. Our results may provide insight into the early pathogenetic mechanisms of AD.

Key words: axonal transport; glutamate; amyloid -protein; actin; Ca²⁺; cultured hippocampal neurons

---

Received Feb 11, 2003; revised August 11, 2003; accepted August 14, 2003.

This article has been cited by other articles:

				K. A. Irvine and W. F. Blakemore Remyelination protects axons from demyelination-associated axon degeneration Brain, June 1, 2008; 131(6): 1464 - 1477. [Abstract] [Full Text] [PDF]

				B. W. Bernstein, H. Chen, J. A. Boyle, and J. R. Bamburg Formation of actin-ADF/cofilin rods transiently retards decline of mitochondrial potential and ATP in stressed neurons Am J Physiol Cell Physiol, November 1, 2006; 291(5): C828 - C839. [Abstract] [Full Text] [PDF]

				Y. Rui, P. Tiwari, Z. Xie, and J. Q. Zheng Acute Impairment of Mitochondrial Trafficking by beta-Amyloid Peptides in Hippocampal Neurons J. Neurosci., October 11, 2006; 26(41): 10480 - 10487. [Abstract] [Full Text] [PDF]

				L. Heredia, P. Helguera, S. de Olmos, G. Kedikian, F. Sola Vigo, F. LaFerla, M. Staufenbiel, J. de Olmos, J. Busciglio, A. Caceres, et al. Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease. J. Neurosci., June 14, 2006; 26(24): 6533 - 6542. [Abstract] [Full Text] [PDF]

				M. T. Maloney, L. S. Minamide, A. W. Kinley, J. A. Boyle, and J. R. Bamburg {beta}-Secretase-Cleaved Amyloid Precursor Protein Accumulates at Actin Inclusions Induced in Neurons by Stress or Amyloid {beta}: A Feedforward Mechanism for Alzheimer's Disease J. Neurosci., December 7, 2005; 25(49): 11313 - 11321. [Abstract] [Full Text] [PDF]

				H. Takeuchi, T. Mizuno, G. Zhang, J. Wang, J. Kawanokuchi, R. Kuno, and A. Suzumura Neuritic Beading Induced by Activated Microglia Is an Early Feature of Neuronal Dysfunction Toward Neuronal Death by Inhibition of Mitochondrial Respiration and Axonal Transport J. Biol. Chem., March 18, 2005; 280(11): 10444 - 10454. [Abstract] [Full Text] [PDF]

				J. M. Edgar, M. McLaughlin, D. Yool, S.-C. Zhang, J. H. Fowler, P. Montague, J. A. Barrie, M. C. McCulloch, I. D. Duncan, J. Garbern, et al. Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia J. Cell Biol., July 5, 2004; 166(1): 121 - 131. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help