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Y. Kishimoto, C. Yabuta, M. Azuma; FK962 Enhances Axonal Regeneration in Cultured Rat Trigeminal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3406.
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Innervation of ocular tissues by central and peripheral nerves is essential for normal physiological function. Disruption of this innervation causes serious ocular diseases. For example, amputation of trigeminal nerve leads to decreased corneal sensitivity and dry eye, and degeneration of the optic nerve from high intra-ocular pressure leads to profound visual defects. N-(1-acetylpiperidin-4-yl)-4-fluorobenzamide (FK962) causes release of neurotrophic factors, and is a putative cognitive enhancer. The purposes of the present experiments were to determine if: 1) FK962 induces axonal elongation in cultured trigeminal ganglion cells, and 2) FK962 lengthens axons in an in vitro model of axotomy.
Trigeminal ganglion cells (neuronal + Schwann cells) or isolated neuronal cells were cultured for 24 hours with or without FK962. Cells were fixed, labeled with antibody for neurofilament and substance P, and observed with a fluorescence microscope. An axotomy model was produced by culturing trigeminal ganglion cells with nerve growth factor (NGF) for 48 hours. Axons were then transected with tweezers, cultured with FK962 for an additional 24 hours, and the cells were immunostained as above.
In cultured neurons, FK962 induced sprouting and elongation of axons co-cultured with or without Schwann cells. In the axotomy model without added FK962, axons distal to the transected nerve terminals rapidly disappeared, and with cultured time, the axons then regenerated. Addition of FK962 further enhanced regeneration of axons in the axotomized trigeminal ganglion cells.
FK962 enhanced sprouting and regeneration of axons in both normal and transected axons. The effect of FK962 is at least partially due to direct action on neurons. Concomitant indirect action by FK962 on Schwann cells may also be important for supporting the neurons.
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