Morphology of embryonic neostriatal cell suspensions transplanted into adult neostriata

McAllister, James P.; Walker, Paul D.; Zemanick, Mark C.; Weber, Axel; Kaplan, L.I.; Reynolds, Milton

doi:10.1016/0165-3806(85)90051-3

Cited by 66 publications

(6 citation statements)

References 17 publications

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“…Previous studies in the intact striatum have shown that it is the spines of medium size densely spiny neurons, as identified by Golgi-impregnation (Frotscher et al, 1981) or by Golgiimpregnation and retrograde transport of horseradish peroxidase from the substantia nigra (Somogyi et al, 1981;Dub6 et al, 1988), that are one of the major targets of corticostriatal fibres. Golgi-impregnated examples of this same class of neuron (which probably constitutes in the region of 90% of all striatal neurons) have been identified in striatal grafts of the type used here (McAllister et al, 1985;Clarke et al, 1988). Thus, although there is more than one type of spine-bearing neuron in the rat striatum (Chang et al, 1982) it is highly likely that mediumsize spiny neurons in the grafted tissue are among the targets of the corticostriatal fibres.…”

Section: Discussionmentioning

confidence: 61%

“…Tissue obtained from the foetal striatal eminence survives grafting to the excitotoxically lesioned striatum of adult recipient rats. These grafts grow to establish a neuron-rich tissue within the neuron-depleted area and exhibit some morphological and histochemical features similar to those of the normal striatum (Isacson et al, 1984(Isacson et al, , 1985McAllister et al, 1985). Previous light microscopic studies (Pritzel et al, 1986;Clarke et al, 1988;Wictorin et al, 1988aWictorin et al, ,b, 1989a have shown that all principal afferent inputs to the striatum (i.e.…”

Section: Introductionmentioning

confidence: 96%

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Host Corticostriatal Fibres Establish Synaptic Connections with Grafted Striatal Neurons in the Ibotenic Acid Lesioned Striatum

Wictorin

Clarke

Bolam

et al. 1989

Eur J of Neuroscience

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The connections between host corticostriatal afferents and neurons in intrastriatal grafts of foetal striatal tissue have been studied with electron microscopic immunocytochemistry using Phaseolus vulgaris leucoagglutinin (PHA-L) as a label of the host corticostriatal fibres. Adult rats with unilateral ibotenic acid lesions of the head of the caudate putamen received foetal cell suspension grafts from E14-15 rat embryos into the lesioned striatal area. Ten months after transplantation, multiple iontophoretic injections of PHA-L were made into the host frontal cortex. These injections labelled large numbers of corticostriatal fibres which extended across the graft - host border to form a rich axonal network mainly in the peripheral portions of the grafts. At the ultrastructural level a total of 134 PHA-L-labelled terminals were identified to form asymmetric synaptic contacts with neurons within the grafts. Of these contacts, 83% were in contact with dendritic spines, 12% with dendritic shafts, and 5% with small shafts or spines. The synaptic contacts were similar to those identified in intact regions of the host striatum that were spared by the lesion. However, the synapses in the host striatum were almost exclusively in contact with spines (98%). These results demonstrate that the corticostriatal projection, which constitutes a major source of afferent control in the normal striatum, not only extends axons into the intrastriatal striatal grafts, but also establishes synaptic connections with the implanted neuronal elements.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 96%

Host Corticostriatal Fibres Establish Synaptic Connections with Grafted Striatal Neurons in the Ibotenic Acid Lesioned Striatum

Wictorin

Clarke

Bolam

et al. 1989

Eur J of Neuroscience

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“…the degree of development of adjoining P and NP zones in the The first alternative is not in accord with the age predicted by grafts is equivalent. In fact, based on the reduced density of the calbindin-positive zones in the same grafts, and the second spines on Go&-impregnated medium-sized neurons in the grafts, and third do not fit the low AChE activity, especially the near McAllister et al (1985) concluded that the grafted neurons are absence of TH-like immunoreactivity in the NP zones.…”

Section: The Np Regionsmentioning

confidence: 97%

Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization

1989

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Fetal striatal grafts display a striking modularity of composition. With acetylcholinesterase (AChE) histochemistry, the tissue of such grafts can be divided into regions with strong AChE staining of the neuropil and regions in which AChE staining of the neuropil is weak. In the experiments reported here, we reexamined the nature of this modularity. Striatal grafts were made by injecting dissociated cells of E15 ganglionic eminence into the striatum of adult rats, which 7 days before had recived intrastriatal deposits of ibotenic acid. Some donors had been exposed to 3H-thymidine at E11-E15. After 9-17 month survivals, the anatomical organization of the grafts was studied by histochemistry, immunohistochemistry, and autoradiography. In every graft, the AChE-rich regions formed patches (P regions) in a larger AChE-poor surround (NP regions). Neurons labeled with 3H-thymidine appeared in both P and NP regions, suggesting that donor cells were distributed in each type of region and that neither type of tissue, P or NP, was composed exclusively of host tissue. In the AChE-rich P regions, markers characteristic of normal perinatal and mature rat striatum were expressed by medium-sized cells: calcium-binding protein (calbindin D28k) immunostaining, metenkephalin (mENK) immunostaining, and, more rarely, somatostatin (SOM) immunostaining. In the NP regions, however, medium-sized cells expressing calbindin and mENK immunostaining were very rare, and there was an abundance of neuronal types not found in normal mature striatal tissue. These included (1) large, multipolar, calbindin-positive neurons with well-ramified, densely stained dendrites, (2) large, SOM-positive neurons with prominent dendritic trees, and (3) mENK-positive cells smaller than typical striatal, medium-sized, mENK-immunoreactive neurons. In Nissl stains, the AChE-rich P regions resembled the normal striatum of mature animals, whereas the AChE-poor NP regions did not. These findings suggest that the P regions of fetal striatal grafts achieve a phenotypy similar to that of normal striatum at maturity and during much of postnatal development. The dominant expression of perikaryal calbindin-like immunoreactivity in the P regions further suggests that these zones have a high proportion of tissue resembling striatal matrix. By contrast, expression of marker antigens in the NP zones of the grafts suggests that these zones are predominantly composed of nonstriatal tissue or that they have the phenotypy of immature striatum intermixed with some nonstriatal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Fetal striatal cell transplants into the neostriatum have been shown to partially reverse the motor deficits (Deckel et al, 1983(Deckel et al, , 1986a(Deckel et al, , b, 1987Isacson et al, 1984Isacson et al, , 1986 and biochemical changes (Isacson et al, 1984(Isacson et al, , 1985 that occur following chemical lesions in the rat caudate nucleus. Anatomical studies have also demonstrated that striatal grafts exhibit Golgi-impregnated neurons characteristic of the neostriatum (McAllister et al, 1985) and form afferent and efferent connections with host tissue (Pritzel et al, 1986). Although light-microscopic observations have provided information about the general histological features of striatal grafts (McGeer et al, 1984;Isacson et al, 1985Isacson et al, , 1986Deckel et al, 1986a), little is known about the synaptic organization of implanted fetal striatal cells that might underlie the functional effects and connectivity with host observed in the studies mentioned above.…”

Section: Neuronal Organizationmentioning

confidence: 99%

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

1988

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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.

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Morphology of embryonic neostriatal cell suspensions transplanted into adult neostriata

Cited by 66 publications

References 17 publications

Host Corticostriatal Fibres Establish Synaptic Connections with Grafted Striatal Neurons in the Ibotenic Acid Lesioned Striatum

Host Corticostriatal Fibres Establish Synaptic Connections with Grafted Striatal Neurons in the Ibotenic Acid Lesioned Striatum

Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization

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

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