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Sabeluzole, a memory-enhancing molecule, increases fast axonal transport in neuronal cell cultures.

Authors
  • Geerts, H
  • Nuydens, R
  • Nuyens, R
  • Cornelissen, F
  • De Brabander, M
  • Pauwels, P
  • Janssen, P A
  • Song, Y H
  • Mandelkow, E M
Type
Published Article
Journal
Experimental neurology
Publication Date
Jul 01, 1992
Volume
117
Issue
1
Pages
36–43
Identifiers
PMID: 1377635
Source
Medline
License
Unknown

Abstract

Morphological rearrangements, such as synapse number changes, have been observed in the adult mammalian brain after various experimental paradigms of learning and behavioral experience. The role of axonal transport in the physical translocation of material during this form of brain plasticity has not been fully appreciated. We show here by quantitative video microscopy that sabeluzole (R58735), a new memory-enhancing drug in humans, effectively increases fast axonal transport in rat neuronal cell cultures. Long-term incubation (24 hr) with sabeluzole in the concentration range between 0.1 and 1 microM increases both velocity and jump length of saltatory movements maximally by 20-30% in embryonic hippocampal neurons. Acute treatment only increases the velocity by 15-20%. Furthermore, the inhibition of axonal transport by 0.1 mM vanadate in N4 neuroblastoma cells is reversed by 1 microM sabeluzole. Observations on the kinesin-induced microtubule mobility in a reconstituted system show a 10% enhancement by sabeluzole at an optimal concentration of 2 microM, but no increase in kinesin ATPase activity. To our knowledge, this is the first pharmacological compound shown to increase fast axonal transport. The mechanism of fast axonal transport enhancement is discussed as a rationale for new therapeutic treatment in neuropathology.

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