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PubMed1992

Compartmental distribution of ventral striatal neurons projecting to the mesencephalon in the rat.

The ventral striatum is characterized by an intricate neurochemical compartmentation that is reflected in the distribution of most of its afferent fiber systems. In the present study, the compartmental relationships of ventral striatal neurons projecting to the mesencephalon were studied by combining tract tracing with the immunohistochemical localization of leu-enkephalin. Injections of the retrograde tracer cholera toxin subunit B were placed at various sites in the ventral mesencephalon. The anterograde tracer Phaseolus vulgaris leucoagglutinin was injected in single compartments in the rostrolateral part of the nucleus accumbens. The projections from the ventral striatum to the dopaminergic cell groups in the ventral mesencephalon and those to the substantia nigra pars reticulata originate from distinct subpopulations of ventral striatal neurons that respect neurochemically defined compartmental boundaries. In the "shell" of the nucleus accumbens, neurons that project to the dopaminergic cell groups are located outside areas of high cell density and weak enkephalin immunoreactivity (ENK-IR). Rostrolaterally in the "core" of the nucleus accumbens, neurons inside large areas of strong ENK-IR surrounding the anterior commissure project to the dorsomedial part of the substantia nigra pars reticulata, whereas neurons outside these areas innervate the ventral tegmental area and/or the medial part of the substantia nigra pars compacta. By contrast, more caudally in the dorsal part of the nucleus accumbens and in the ventral part of the caudate-putamen, the relationships are reversed: neurons in- or outside small patches of strong ENK-IR project respectively to the pars compacta or the pars reticulata of the substantia nigra. Since the thalamic and cortical afferents of the ventral striatum are compartmentally ordered as well, the present results imply that through the ventral striatal compartments information from disparate combinations of cortical and thalamic sources may be conveyed to distinct mesencephalic targets. The component of the ventral striatomesencephalic system reaching the dopaminergic cell groups A10, A9, and A8 may modulate the dopaminergic input to virtually the entire striatum. The other component can, by way of the pars reticulata of the substantia nigra, participate in nigrothalamic and nigrotectal output pathways of the basal ganglia.

Animals↗
PubMed1982

Significance of glycosidases in lipid and carbohydrate metabolism II. Studies in the mesencephalon of fresh water turtle (Lissemys punctata).

The contribution deals with histochemical localization of alpha-glucosidase, beta-glucosidase, beta-galactosidase and beta-glucuronidase in the mesencephalon of fresh water turtle. These enzymes demonstrate strong activity in all the myelinated fibers. Neuronal elements of nucleus ruber, nucleus isthmi, torus semicircularis, third and fourth cranial nerve nuclei, nucleus profundus mesencephali etc. demonstrate variable activity. Interestingly enough, there is parallel localization of all these enzymes in nuclei and tracts of mesencephalon. Further, the pattern of phospholipids and neutral lipids localization is almost identical to that of glycosidases. Since lipids and carbohydrates are rich source of energy in the central nervous system, and these enzymes are involved in their breakdown, their possible role in nerve cells and fibers of mesencephalon of turtle has been discussed.

Animals↗
PubMed1995

Survival of and 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity against dopaminergic neurons in coculture of rat mesencephalon with their target on non-target regions.

It is known that dopaminergic neurons in the substantia nigra of the mesencephalon mainly project to the corpus striatum and neocortex, while the hippocampus receives major cholinergic projection from the septum. In the present study, the ventral mesencephalon was cocultured with target regions of its dopaminergic neurons, the striatum and neocortex, and with non-target regions, the hippocampus, thalamus, colliculus and cerebellum, using embryonic day-17 (E17) rats. Thus, the effects of coculture on the survival and the 1-methyl-4-phenylpyridnium (MPP+) neurotoxicity of dopaminergic neurons were investigated. The numbers of viable dopaminergic neurons were enhanced in coculture not only with corpus striatum or neocortex, but also with hippocampus or cerebellum. However, the survival of dopaminergic neurons cocultured with thalamus and colliculus were almost the same as those of controls. These findings suggest that putative factor(s), possibly target-derived neurotrophic factor(s), emerging from the regions cocultured with ventral mesencephalon can influence the dopaminergic neurons resulting in the augmentation of survival. Cocultivation with all the regions studied failed to protect dopaminergic neurons from MPP+ neurotoxicity. The results suggest that even though the survival of dopaminergic neurons was supported by coculture, the action of MPP+, an exogeneous substance, surpassed the supporting capacity of the coculture conditions.

1-Methyl-4-phenylpyridinium↗
PubMed1997

A morphometric evaluation of morphological types of microglia and astroglia in human fetal mesencephalon.

Quantitative changes associated with the differentiation of microglial and astroglial cells in 48 fetal mesencephalons between 8 and 22 week of gestation (GW) were studies. Using lectin (RCA-1) labelling, two morphological types of RCA-1 positive cells, ameboid microglia (AM) and ramified microglia (RM) were identified on the basis of the cell body shape and the configuration of cytoplasmic processes. Astrocytes (AS) were identified by immunocytochemical labelling of GFAP. Measurements of microglial and astroglial cells were carried out in mesencephalon tectum and tegmentum under the microscope in sequential segments corresponding to equal sized non-overlapping areas. The quantitative data about concerning the number and percentage distribution of AM, RM and AS from each of the grid-quartiles were analyzed. The study revealed a time-sequence of appearance, characteristic pattern of distribution along perpendicular and longitudinal axes originating from aqueduct and changes in percent distribution of both types of microglial cells and astrocytes. Ameboid type of microglia was already present in 8 GW fetus in tectum (22.5 cells/mm2) and in tegmentum (10.2 cells/mm2). During the fetal development the number of AM peaked about 8-9 GW in tectum, accounting for 29 cells/mm2 close to aqueduct, and about 11-12 weeks in tegmentum, reaching 10.2-11 cells/mm2 close to aqueduct. As the fetus development advanced, the number of AM cells both in tectum and tegmentum was slowly dropped down reaching about 1.0 cells/mm2 in 20-22 GW. The ramified microglial cells as well as astroglial cells emerged in the fetal mesencephalon after 11 GW. A quantitative study also revealed a rapid increase in the density of RM in 13-16 GW (6.3 cells/mm2-close to aqueduct) and AS cells in 13-16 GW (36 cells/mm2-close to aqueduct) and later a decrease in cell number was observed. Similarly to AM, changes in the number of RM and AS cells were stabilized to about 20-22 GW. The percentage distribution of each type of microglia and astrocyte cells both in tectum and tegmentum differed markedly during the fetus development depending on the localization along the axes.

Astrocytes↗
PubMed1998

Distribution of neurofilaments in the telencephalon and mesencephalon of the adult and developing Gallotia galloti lizard.

The location and chronology during development of the immunoreactivity due to the presence of neurofilaments (NF) in telencephalon and mesencephalon of the lizard Gallotia galloti has been studied. For this purpose we have used two antibodies recognizing both phosphorylated and non phosphorylated neurofilaments (NF), a polyclonal Ab (NF 005), and a commercial monoclonal antibody (NF-200). The study was completed by using the Bielschowsky technique. During ontogeny, the anti-NF 005 immunoreactivity appeared at E40 in some tracts in mesencephalon and increased in intensity in isolated nerve fibers, tracts and commissurae till adult. However, a weak staining appeared in some neurons. In telencephalon, the reactivity was detected only in adult specimens. It was clearly more abundant in mesencephalon than in telencephalon, which could indicate that a greater complexity and functional importance exist in the lizard midbrain in relation to other primitive regions as the basal nuclei and cortical areas. In contrast to young specimens, the monoclonal anti-NF 200 was detected in neuronal perikarya, dendrites and axons in adults. Thus, in lizards, both antibodies highly recognized phosphorylated and non-phosphorylated forms of proteins of NF (NF-H). In mammals, these forms of proteins are implicated in axonal maturation. The presence of these NF in reptiles, identified for the first time, proved to be phylogenetically stable. The anti-NF immunoreactivity distribution occurs both caudo-rostrally and from the ventral to the dorsal regions.

Animals↗
PubMed1976

Histochemical mapping of dopamine neurons and fiber pathways in dog mesencephalon.

A topographic mapping of dopamine (DA)-containing neurons and fibers was done mainly in the mesencephalon of the dog using the fluorescent histochemical technique of Falck and Hillarp. The extensive DA neuron system was found to be located in the ventral and medial regions of the mesencephalon; the pars compacta of the substantia nigra, the area almost corresponding to the ventral tegmental area of Tsai (which consists of three groups, a caudal, the nucleus parabrachialis pigmentosus, a ventral, the nucleus paranigralis and a rostral, the caudal part of the nucleus tegmentalis ventralis of Tsai), the nucleus linearis of the raphe, and the mesencephalic reticular formation. The nigro-neostriatal projection can be traced in the non-treated or nialamide plus L-dopa treated puppies without the lesion-degeneration technique. Most fibers arising from these DA cell groups assemble at the prerubral area and ascend just dorsal to the medial forebrain bundle. Most fibers turn laterally at the lateral hypothalamus and enter the neostriatum via the dorsal part of the subthalamic nucleus, the zona incerta and the capsula interna. These findings show that the distribution of DA neurons and the nigro-neostriatal pathway are fundamentally similar to those in other mammals. In this study, the processes of the nigral and paranigral DA neurons have been demonstrated to project into the pars reticulata in the dog.

Animals↗
PubMed1987

Segment-related, mosaic neurogenetic pattern in the forebrain and mesencephalon of early chick embryos: I. Topography of AChE-positive neuroblasts up to stage HH18.

Histochemical mapping of AChE-positive neuroblasts in sectioned and whole-mounted preparations of the chick embryo mesencephalon and prosencephalon allows a correlation of early neural tube morphogenesis (segmentation, longitudinal compartmentation) with the heterochronic pattern of neurogenesis. One significant finding is that the initial appearance of neuroblasts in the forebrain does not follow neuromeric segmentation, but evolves in parallel with it. Early neuroblasts appear as separate, distinct groups within specific matrix territories at the center of the transverse neuromeric segments. Neighbouring segments display different spatiotemporal patterns of neurogenesis. Overall gradients of differentiation in the rostrocaudal and ventrodorsal directions are absent, whereas a clear-cut segment-related, mosaic pattern becomes evident. Notwithstanding this, gross regularities of heterochrony in the neurogenetic behavior of the different segments lead to a definition of elemental longitudinal compartments of the forebrain and mesencephalon (floor, paramedian, basal, and alar regions) on the basis of precocious differentiation of the basal region and retarded differentiation of the paramedian and alar regions.

Acetylcholinesterase↗
PubMed1989

GABA-like immunoreactivity of neurons in the chicken diencephalon and mesencephalon.

The chick brain is a useful model system for studying the ontogeny and phylogeny of neural circuitry, especially that of the visual system. In this study the distribution of cells and processes showing GABA-like immunoreactivity (GABA+) in the diencephalon and mesencephalon of the posthatch chick was determined immunohistochemically with a polyclonal antibody to GABA and compared with the results of similar studies in mammals. Most of the small GABA+ cells were found in the chick visual centers such as the nucleus lateralis anterior, suprachiasmatic nucleus, ventral lateral geniculate, optic tract, dorsolateralis anterior pars lateralis, lentiformis mesencephali, ectomammillary nucleus, area pretectalis, and the optic tectum. Large GABA+ cells were found in the following nuclei: reticularis superior, posteroventralis thalami, subpretectalis, isthmi pars magnocellularis, interstitio-pretectosubpretectalis, mesencephalicus lateralis pars dorsalis. These large cell-containing nuclei receive projections from visual or auditory centers. GABA+ axons were found throughout the diencephalon and mesencephalon but were especially prominent in the ansa lenticularis, fasciculus medialis longitudinalis, and optic tract. The distribution of GABA+ cells in the chick is more widespread than in rodents and exhibits an increased association with the visual centers suggesting a correlation with the specialized visual requirements of the bird.

Animals↗
PubMed1990

Topography and synaptology of mamillary body projections to the mesencephalon and pons in the rat.

The anterograde and retrograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) was used to study the anatomical organization of descending projections from the mamillary body (MB) to the mesencephalon and pons at light and electron microscopic levels. Injections of WGA-HRP into the medial mamillary nucleus resulted in dense anterograde and retrograde labeling in the ventral tegmental nucleus, while injections in the lateral mamillary nucleus resulted in dense anterograde labeling in the dorsal tegmental nucleus pars dorsalis and dense anterograde and retrograde labeling in the pars ventralis of the dorsal tegmental nucleus. Anterogradely labeled fibers in the mamillotegmental tract diverged from the principal mamillary tract in an extensive dorsocaudally oriented swath of axons which extended to the dorsal and ventral tegmental nuclei, and numerous axons turned sharply ventrally and rostrally to terminate topographically in the dorsomedial nucleus reticularis tegmenti pontis and rostromedial pontine nuclei. The anterograde labeling in these two precerebellar relay nuclei was distributed near the midline such that projections from the lateral mamillary nucleus terminated mainly dorsomedial to the terminal fields of projections from the medial mamillary nucleus. In the dorsal and ventral tegmental nuclei, labeled axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions primarily with small diameter dendrites and to a lesser extent with neuronal somata. A few labeled terminals contained pleomorphic vesicles and formed symmetric synaptic junctions with dendrites and neuronal somata. Labeled axon terminals were also frequently found in synaptic contact with retrogradely labeled dendrites and neuronal somata in the dorsal and ventral tegmental nuclei. These findings indicate that neurons in the dorsal and ventral tegmental nuclei are reciprocally connected with MB projection neurons. In the nucleus reticularis tegmenti pontis and medial pontine nuclei, labeled axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions primarily with small diameter dendrites. The present study demonstrates that projections from the medial and lateral nuclei of the MB are topographically organized in the mesencephalon and pons. The synaptic morphology of mamillotegmental projections suggests that they may have excitatory influences primarily on the distal dendrites of neurons in these brain regions.

Afferent Pathways↗
PubMed1992

Immunohistochemical localization of nicotinic acetylcholine receptor subunits in the mesencephalon and diencephalon of the chick (Gallus gallus).

Monoclonal antibodies against two alpha-bungarotoxin-binding subunits (alpha 7 and alpha 8) of the nicotinic acetylcholine receptors (nAChRs) were used as immunohistochemical probes to map their distribution in the chick diencephalon and mesencephalon. The distribution of the alpha 7 and alpha 8 nAChR subunits was compared to the distribution of immunoreactivity produced by a monoclonal antibody against the beta 2 structural subunit of the nAChRs. Structures that contained high numbers of alpha 7-like immunoreactive (LI) somata included the intergeniculate leaflet, nucleus intercalatus thalami, nucleus ovoidalis, organum paraventricularis, nucleus rotundus, isthmic nuclei, nucleus trochlearis, oculomotor complex, nucleus interstitio-pretecto-subpretectalis, stratum griseum centrale of the optic tectum, and nucleus semilunaris. Neuropil staining for alpha 7-LI was intense in the nucleus dorsomedialis hypothalami, nucleus geniculatus lateralis ventralis, griseum tecti, isthmic nuclei, nucleus lentiformis mesencephali, nucleus of the basal optic root, and stratum griseum et fibrosum superficiale of the tectum. High numbers of alpha 8-LI somata were found in the stratum griseum et fibrosum superficiale of the tectum and the nucleus interstitio-pretecto-subpretectalis, and intense neuropil staining for alpha 8-LI was found in the dorsal thalamus, nucleus geniculatus lateralis ventralis, lateral hypothalamus, griseum et fibrosum superficiale of the tectum. High numbers of beta 2-LI somata were found only in the nucleus spiriformis lateralis, whereas neuropil staining for beta 2-LI was intense in the nucleus geniculatus lateralis ventralis, nucleus suprachiasmaticus, nucleus lateralis anterior, nucleus habenularis lateralis, area pretectalis, griseum tecti, nucleus lentiformis mesencephalis, nucleus externus, and nucleus interpeduncularis, and in the stratum griseum centrale, stratum griseum et fibrosum superficiale, and stratum opticum of the tectum. These results indicate that there are major disparities in the localization of the alpha-bungarotoxin-binding alpha 7 and alpha 8 nAChR subunits and the beta 2 structural nAChR subunit in the chick diencephalon and mesencephalon. These nAChR subunits appear, however, to coexist in several regions of the chick brain.

Animals↗
PubMed2001

Influence of time in culture and BDNF pretreatment on survival and function of grafted embryonic rat ventral mesencephalon in the 6-OHDA rat model of Parkinson's disease.

Embryonic midbrain can be maintained as free-floating roller tube cultures prior to grafting in experimental Parkinson's disease. We examined the influence of pregrafting culture time and pretreatment with brain-derived neurotrophic factor on graft survival and function. Cultures were prepared from solid pieces of embryonic (E14) rat ventral mesencephalon and maintained 4, 8, or 12 days in vitro with or without brain-derived neurotrophic factor (100 ng/ml) and grafted into the striatum of 6-hydroxydopamine-lesioned rats. Graft survival and function were evaluated by amphetamine-induced rotation behavior, number of tyrosine hydroxylase-immunoreactive neurons, striatal reinnervation, and graft volume. Rats receiving untreated tissue cultured for 4 or 8 days displayed no differences in graft quality, while grafts from 12-day-old cultures contained significantly fewer (P < 0.05) tyrosine hydroxylase-immunoreactive neurons (340 +/- 97, 267 +/- 92, and 62 +/- 19) and displayed a lower survival rate (9.6 +/- 2.7, 7.9 +/- 2.7, and 2.6 +/- 0.8% for 4, 8, and 12 days in vitro, respectively). Only rats grafted with 4- and 8-day-old cultures recovered significantly (P < 0.05) from lesion-induced rotations (69.4 +/- 18.6, 70.3 +/- 13.9, and 23.2 +/- 12.1% for 4, 8, and 12 days in vitro, respectively). Striatal reinnervation decreased with increasing culture time (P < 0.05). Pretreatment of the cultures with brain-derived neurotrophic factor affected only graft-induced fiber reinnervation, which was reduced even after short culture times. We therefore suggest that a storage period of 8 days is well suited to maintain embryonic rat ventral mesencephalon with the free-floating roller tube culture technique prior to transplantation. BDNF pretreatment as a new strategy to improve graft survival and function, however, was not effective.

Amphetamine↗
PubMed1995

Hitchcock's experimental series of foetal implants for Parkinson's disease: co-grafting ventral mesencephalon and striatum.

Following 4 previous experimental series of foetal implants (mesencephalon) to treat patients with Parkinson's disease subjects (N7) in the fifth series were treated with co-grafts of foetal mesencephalon and striatum implanted stereotactically into the caudate nucleus bilaterally. The clinical outcome, better than in the previous series, included improvements lasting through 18 months follow-up in activities of daily living, clinical neurological motor examination, timed motor tasks, and dyskinesia-with reduction in the patients' need for dopaminergic medication.

Brain Tissue Transplantation↗
PubMed1996

Comparative distribution of NADPH-diaphorase activity and tyrosine hydroxylase immunoreactivity in the diencephalon and mesencephalon of the domestic chicken (Gallus domesticus).

We described the distribution of NADPH-diaphorase-containing neurons in relation to tyrosine hydroxylase immunoreactivity in the diencephalon and mesencephalon of the chicken. In the diencephalon, both markers were found in the lateral hypothalamus, dorsal hypothalamic area, hypothalamic periventricular nucleus, paraventricular nucleus and mamillary area. A close examination showed that the fine distribution of these markers differed slightly, so that they were never observed in the same neurons. In the mesencephalon, NADPH-diaphorase and tyrosine hydroxylase immunoreactivity were found in the ventral pedunculopontine area (nucleus tegmenti pedunculopontinus pars compacta, adjacent areas surrounding the quintofrontal tract and the nucleus mesencephalicus profundus ventralis), the coeruleus complex (locus coeruleus, ventral and dorsal subcoeruleus nuclei), the ventral tegmental area and the central gray. The majority of these neurons contained either diaphorase or tyrosine hydroxylase. Nevertheless, in a few cases both markers appeared to colocalize in the same neuron, typically in large perikarya of the ventral pedunculopontine area.

Animals↗
PubMed1988

Specialized ependyma in the posterior mesencephalon of the chicken: the fine structure of the subtrochlear organ.

A formation of specialized ependymal cells in the posterior mesencephalon of the domestic fowl, designated as the subtrochlear organ, was examined with light-, scanning- and transmission electron microscopy. This organ possessing the form of the letter "V" is located in the ventricular wall of the posterior mesencephalon. Its apex marks the median sulcus, while the arms of the V are directed rostrolaterally. Ependymal cells lining the subtrochlear organ usually project an extremely elongated process into the subependymal region and are classified into three types according to their surface features: (1) cells with a bulb-shaped protrusion that projects into the ventricle, (2) single cilium-bearing cells, and (3) cells with a tuft of cilia. The first type of cell is restricted to the median portion of the subtrochlear organ; its bulb-shaped protrusion contains numerous ribosomes. The second type of cell predominates in the arm (rostrolateral) area; in its apical cytoplasm such ciliary structures as basal body are rarely seen. The third type of cell is usually assembled into several small islands on the arm area; it has many basal bodies and other ciliary structures in the apical cytoplasm.

Animals↗
PubMed1993

Avian photogenic epilepsy and embryonic brain chimeras: neuronal activity of the adult prosencephalon and mesencephalon.

Photogenic genetic epilepsy was studied in an avian model, using either the Fayoumi epileptic chicken (Fepi) or neural chimeras obtained by replacement of embryonic brain vesicles in normal chickens with those of Fepi embryos. In these two kinds of animals motor seizures accompanied by electroencephalographic (EEG) desynchronization and flattening (DF) were evoked by intermittent light stimulation (ILS). In chimeras with only the prosencephalon grafted, motor seizures were less severe but DF remained. ILS-induced DF persisted under paralysis by gallamine triethiodide (Flaxedil). Extracellular recordings were made in the prosencephalon (wulst) and in the mesencephalon (optic tectum) of paralysed animals. Units recorded in the prosencephalon of Fepi and chimeras showed abnormal interictal bursting activity, distinctly different from the non-epileptic Fayoumi heterozygotes (Fhtz) and normal chickens. The mesencephalic units of Fepi and chimeras having both prosencephalon and mesencephalon grafted showed two types of abnormal activities during ILS-induced DF, which were distinct from the non-epileptic chickens: type I neurons displaying early, high sensitivity to ILS followed by a prolonged suppression of activity; type II neurons displaying an early and prolonged suppression of activity. The results are discussed with respect to the brain structures generating ictal and interictal EEG activities and motor seizures.

Animals↗
PubMed1995

Electrophysiological characterization of dopaminergic and non-dopaminergic neurones in organotypic slice cultures of the rat ventral mesencephalon.

The aim of the present study was to characterize electrophysiologically neurones in organotypic cultures of the rat ventral mesencephalon and to compare these results with results published for the same neurones in other types of preparation. Intracellular recordings were obtained in 3- to 8-week-old organotypic slice cultures of the ventral mesencephalon prepared from new-born rats. Dopaminergic neurones were distinguished from non-dopaminergic neurones by staining with the autofluorescent serotonin analogue 5,7-dihydroxytryptamine and briefly viewing the preparation with short exposures to ultraviolet (UV) light (365 nm). Short exposures to UV light did not affect the electrophysiological properties. There were no significant differences between dopaminergic and non-dopaminergic neurones with regard to resting membrane potential or action potential threshold and amplitude, and in both types of neurone spontaneous burst activity and glutamatergic excitatory postsynaptic potentials were seen. There were differences in the following parameters, which can be used to distinguish between the two types of neurone. Dopaminergic neurones had broad action potentials (2-9 ms), high input resistance (mean 81 M omega), were silent or fired spontaneously at a low frequency (0-9 Hz), and no spontaneous GABAA-ergic inhibitory postsynaptic potentials or inward rectification were present. In contrast, non-dopaminergic neurones had fast action potentials (0.6-3.2 ms), low input resistance (mean 32 M omega), were silent or fired spontaneously at relatively high firing frequency (0-28 Hz), and sometimes inhibitory postsynaptic potentials and inward rectification were seen. In the presence of 1 microM tetrodotoxin and 10 mM tetraethylammonium, Ca2+ spikes could be evoked in both dopaminergic and non-dopaminergic neurones. Dopaminergic neurones in 3- to 8-week-old organotypic slice cultures have a number of distinguishing electrophysiological characteristics similar to those recorded in other types of acute or cultured preparations. However, some intrinsic regulatory mechanisms, namely the slow oscillatory potentials, inward rectification and the K+ current, IA, seem to be missing in the cultured neurones.

5,7-Dihydroxytryptamine↗
PubMed1994

Re-initiated growth from mature ventral mesencephalon: an in oculo transplant study of nigrostriatal co-grafts.

The ability of mature dopaminergic neurons derived from ventral mesencephalon to re-initiate growth after making contact with a non-innervated target was studied using the intra-ocular grafting model. Foetal ventral mesencephalic tissue or brain stem including the locus coeruleus area was grafted to the anterior chamber of the eye. Two weeks, 6 weeks or 1 year after the first implantation, foetal striatal tissue was placed in contact with the nigral graft or grafted alone. The size of the transplants was measured through the cornea. The final size of the striatal grafts was significantly larger when placed alone than when co-grafted with 1-year-old or 6-week-old dopaminergic grafts. Striatum grafted together with 2-week-old nigra was larger than when grafted adjacent to mature substantia nigra, but not significantly so. Nerve fibre outgrowth into the iris from the nigral transplants did not increase after maturation, but the re-innervated area of the host iris progressively increased around the locus coeruleus grafts. Ingrowth of tyrosine hydroxylase (TH) immunoreactive nerve fibres into the striatal grafts was studied 6 weeks after the second implantation. TH immunohistochemistry revealed innervation of the striatal piece in all cases, except for the group where striatum alone was grafted. With the short survival time for co-grafts of 6 weeks, TH-positive nerve fibres innervated a larger volume, had a patchy appearance and the density was higher in striatum grafted to 2 week-old nigral transplants than that seen in striatal transplants grafted to mature nigral grafts. The patchy pattern of TH-immunoreactive nerve terminals was also seen in striatum co-grafted with 6-week-old or 1-year-old nigral transplants. No difference in striatal innervation volume was detected between those latter two groups. When striatum was implanted adjacent to mature ventral mesencephalon and grown together for 6 months--the longer survival time--the same dense TH-positive innervation as seen in striatum co-grafted with immature nigral tissue at the shorter survival time was found. Additionally, the nigral part of the co-grafts showed increased TH-immunoreactive nerve fibre density. In conclusion, dopaminergic neurites from mature ventral mesencephalic transplants can re-initiate growth if placed in contact with non-innervated striatal tissue. The nigral grafts do not progressively re-innervate the host iris, while locus coeruleus grafts do. The intra-ocular grafting model can be used to study the in vivo effects of trophic factors on mature dopaminergic neurons.

Aging↗
PubMed1989

Xenografting of fetal pig ventral mesencephalon corrects motor asymmetry in the rat model of Parkinson's disease.

A suspension of cells from embryonic day 21 fetal pig ventral mesencephalon was transplanted into the striatum of 20 immunosuppressed rats with 6-hydroxydopamine-induced lesions of the nigrostriatal dopamine pathway. Of these rats, 15 showed reduction of amphetamine-induced ipsilateral rotation by 9 weeks and complete reversal of rotation by 14-17 weeks. Animals maintained stable reversal of rotations (contralateral direction) until cessation of Cyclosporin A (CyA) treatment at 15-20 weeks. Within 4-9 weeks after CyA removal, these rats showed exclusively ipsilateral rotations during behavioral testing which were comparable to pre-transplant levels, suggesting that the grafts were rejected upon cessation of CyA treatment. Rats were sacrificed and tyrosine hydroxylase (TH) immunohistochemistry was performed at several time points, both on and off CyA, to examine a possible correlation between the degree of rotational behavior and the number of TH-positive surviving grafted cells. Staining showed large numbers (230-12,329) of TH-positive surviving cells in animals displaying a high degree of rotational correction (1.6 to -9.6 net ipsilateral rotations/min) after cessation of CyA treatment. Two control groups, those transplanted with non-neuronal cells from the pig ventral mesencephalon (n = 5) and those receiving only daily CyA injections (n = 4) showed no significant reduction of net ipsilateral rotations throughout the experiment. No TH-positive surviving cells were seen in the one non-neuronal transplant analyzed. This data demonstrates long-term retention of xenografted tissue with immunosuppression and its concomitant restoration of normal motor behavior in the rat model of Parkinson's disease.

Animals↗