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Serotonin fiber innervation of cerebellar cell suspensions intraparenchymally grafted to the cerebellum ofpcd mutant mice

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Abstract

One aspect of integration of implanted neurons into the neuronal circuitry of a defective host brain is the re-establishment of a host-to-graft afferent innervation. We addressed this issue by using the adult cerebellum of ‘Purkinje cell degeneration’ (pcd) mutant mice, which lack virtually all Purkinje cells after postnatal day (P) 45. Purkinje cells constitute one of the cerebellar cell types being innervated by axons of raphé serotonin (5-HT) neurons. In normal mice, 5-HT-immunoreactive fibers are distributed to all cerebellar folia. Following Purkinje cell loss inpcd mice, cerebellar 5-HT-immunoreactive fibers persist. Cerebellar cell suspensions were prepared from embryonic day (E) 11–13 normal mouse embryos and were intraparenchymally grafted into the cerebellum ofpcd mutants either directly or after pre-treatment with 5, 7-dihydroxytryptamine (5,7-DHT) to selectively remove 5-HT cells of donor origin. The state of Purkinje cells and 5-HT axons was monitored in alternate sections by 28-kDa Ca2+-binding protein (CaBP) and 5-HT immunocytochemistry, respectively. Serotonin-immunoreactive axons were seen in the grafts from 5 to 32 days after transplantation. In some of the grafts which had not been pre-treated with 5,7-DHT, a small number of 5-HT-immunoreactive cell bodies was found, indicating that part of the 5-HT fiber innervation of the graft could actually derive from donor cells. On the other hand, in grafts pre-treated with 5,7-DHT, no 5-HT cell bodies were seen in the grafted cerebellum; 5-HT fibre innervation of the grafts occurred, but it appeared to be slightly less robust compared to situations of co-grafted 5-HT cell bodies. These findings suggest that host 5-HT fibers are able to provide afferent innervation to donor cerebellar tissue; the presence of co-grafted 5-HT cells may augment such an innervation.

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Author notes

  1. Bernardino Ghetti M.D.

    Present address: Department of Pathology, Indiana University School of Medicine, Medical Science Building A-142, 635 Barnhill Drive, 46202-5120, Indianapolis, Indiana

Authors and Affiliations

  1. Laboratory of Cellular and Molecular Neuropathology, Department of Pathology, and Program in Medical Neurobiology, Indiana University School of Medicine, 46202, Indianapolis, Indiana

    Lazaros C. Triarhou & Bernardino Ghetti M.D.

  2. Departments of Neurosurgery and Physiology, and Program in Neuroscience, University of Minnesota Medical School, 55455, Minneapolis, Minnesota

    Walter C. Low

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  1. Lazaros C. Triarhou
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  2. Walter C. Low
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  3. Bernardino Ghetti M.D.
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Special issue dedicated to Dr. Morris H. Aprison.

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Triarhou, L.C., Low, W.C. & Ghetti, B. Serotonin fiber innervation of cerebellar cell suspensions intraparenchymally grafted to the cerebellum ofpcd mutant mice. Neurochem Res 17, 475–482 (1992). https://doi.org/10.1007/BF00969895

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