Neuronal organization of fetal striatal grafts in kainate- and sham- lesioned rat caudate nucleus: light- and electron-microscopic observations

Abstract

Behavioral and biochemical studies have suggested that fetal striatal grafts in the adult rat neostriatum can reverse deficits induced by excitotoxic lesions of the host caudate tissue. In this study, fetal day 17-18 striatal grafts were examined at 2, 5-6, 12, and 44-48 weeks following their implantation into saline- or kainic acid-treated host caudate nucleus in order to compare the neuronal organization of the grafts and the host caudate nucleus and to determine whether the differentiation of graft tissue was influenced by the period of implantation or prior lesion of the host caudate nucleus with kainic acid. Compared to host neostriatum, the grafts at the light-microscopic level lacked bundles of myelinated axons and had neurons that were tightly packed in clusters and rich in Nissl substance. Neurons in the grafts were mostly of medium size, had significantly larger cross-sectional areas, and more frequently exhibited indented nuclei than host caudate neurons. At the electron-microscopic level, grafts 2 weeks following implantation contained many features seen in the normally developing neostriatum, such as growth cones, immature synapses, and degenerating profiles. Grafts appeared mature by 5-6 weeks and contained at least 6 types of neurons and 8 types of axon terminals, which formed synapses with cell bodies, dendrites, spines, and axon initial segments. Both symmetric and asymmetric synapses were found within the grafts. The density of synapses was significantly lower in all the transplants than in host tissue, with the exception of the 5-6 week grafts, where values were statistically comparable to host caudate. A significantly higher proportion of axodendritic synapses was present in the graft neuropil than in the caudate nucleus. The lengths of the synaptic junctions in the grafts were the same as those in the neostriatum. There was little qualitative or quantitative difference in synaptic organization between transplants in kainic acid and sham-lesioned host, with grafts in both host treatment conditions exhibiting the same synaptic density and proportion of axodendritic/axospinous synapses. The development of a high differentiated ultrastructure within striatal grafts is consistent with recent anatomical evidence showing interconnections between striatal grafts and host-lesioned caudate nucleus. Although graft neuropil shows striking similarities in neuronal organization to the caudate nucleus, it also exhibits some distinct differences that may have implications for understanding the functional properties of fetal striatal grafts in animal models of Huntington's disease.

Postnatal Development of the Rat Neostriatum: Electrophysiological, Light- and Electron-Microscopic Studies

“…A similar dendritic immaturity has been reported for grafted neostriatal neurons which also possess a reduced density of dendritic spines even after many months of maturation in the host brain [DiFiglia et al, 1988;Walsh et al, 1988;Wilson et al, 1990b;Xu et al, 1992;Zemanick et al, 1987].…”

Maturation and Fine Structure of Thalamic Reticular Neurons Transplanted into the Adult Rat CNS

“…in 27], In many studies, as in the present one, a lack of organotypy or even of specific segregation of cell types was observed [8,[28][29][30], Some clustering of cells with a common origin or fate has been reported, however, for striatal [26,[31][32][33][34][35] and cerebellar transplants [4], In the striatal and cerebellar transplants, primordia clearly contained a large number of neuroepithelial cells and neuroblasts which had not yet undergone, or ended their migration. Neurons transplanted as a cell suspension before or at the migratory stage may be capable of recognition and/or tropic activity that is lost at later stages of development.…”

Striatal dopaminergic afferents concentrate in GDNF-positive patches during development and in developing intrastriatal striatal grafts

“…Intrastriatal striatal grafts are interesting experimental models which allow the study of the anatomical integration of fetal neurons in lesioned central nervous system of adults, and have also been proposed as a possible therapeutic approach for Huntington's disease (DiFiglia et al, 1988;Graybiel et al, 1989;Wictorin et al, 1989aWictorin et al, , 1989bLabandeira-García et al, 1991Liste et al, 1997). In fact, striatal grafts implanted in the excitotoxically lesioned striatum, grow, establish connections with the host tissue, and ameliorate the functional deficits induced by the lesion (Deckel et al, 1983;Isacson et al, 1984;Dunnet et al, 1988;Labandeira-García et al, 1991.…”