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Journal of Neuroscience, Vol 11, 1515-1523, Copyright © 1991 by Society for Neuroscience
The effect of tau antisense oligonucleotides on neurite formation of cultured cerebellar macroneurons
A Caceres, S Potrebic and KS Kosik
Department of Neurology (Neuroscience), Harvard Medical School, Boston, Massachusetts.
Tau, a microtubule-associated protein (MAP) enriched in axons, may have a
role in the generation and maintenance of an axonal morphology. Neurons
from embryonic day 15 rat cerebellum in culture elaborate two
morphologically distinct neurite populations--one with nontapering,
elongated axonlike neurites and the other with tapered dendritelike
neurites that branch frequently and are selectively stained with antibodies
to MAP2. Tau antisense oligonucleotides were utilized in two ways: (1)
continuous application of antisense every 24 hr for variable periods of
time or (2) application of antisense that was delayed until neurite
differentiation was underway. In both cases, 24 hr after the administration
of the antisense, tau protein was not detected immunocytochemically. When
the antisense was given continuously directly after plating, the neurites
persisted as simple minor outgrowths. When antisense was added 72 hr after
plating, axonlike neurites were lost, while the remaining neurites
continued to grow and increase in complexity. We concluded that the initial
establishment of an elongated axonlike neurite is a prerequisite for
further neurite maturation; however, once the axon is established, the
remaining neurites are able to grow independently and assume a tapered
dendritelike appearance.
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