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At least 19 recordsLinked to original sources
PubMed1992

Differential effects of conditioned and unconditioned stress on the neurotensin content of dopamine cell body groups of the ventral mesencephalon.

The findings of this study extend the observations of Deutch et al. who suggested that NT in the ventral mesencephalon may be involved in the environmentally elicited activation of selectively responsive populations of mesotelencephalic dopamine neurons. The unconditioned response of NT-LI to electric footshock was observed only at an intensity of 500 microA and only in the lateral subdivision of the VTA. The selective effect of footshock stress on the NT content of a specific cell body group of the ventral mesencephalon suggests that NT mechanisms in the lateral VTA may, in part, underlie the stress-induced activation of dopamine neurons that originate in the lateral VTA. However, it should be noted that populations of dopamine neurons are activated by footshock intensities less than 500 microA, while NT concentrations of mesencephalic dopamine cell body groups are not altered by these shock intensities. The disparity weakens the possibility of a role for NT in the stress-induced activation of brain dopamine neurons unless NT mechanisms may be involved in transducing the effects of higher intensity stressors versus low intensity stressors. However, it should be noted that changes in the concentration of NT-LI represent an endpoint of unknown sensitivity and functional significance and best serve as an initial approximation of the effects of a manipulation on NT-containing neurons. It is plausible that NT mechanisms in the ventral mesencephalon may act in concert with other neuropeptides such as substance P and Met-enkephalin to transduce the effects of stressors on alterations in the activity of mesotelencephalic dopamine neurons that originate in the ventral mesencephalon. An examination of the effects of footshock stress on the content of prepro-NT mRNA in the dopamine cell body groups of the ventral mesencephalon would be of interest in assessing whether stress enhances NT gene expression or alters the characteristics of release of this neuropeptide in the ventral mesencephalon. Lacking NT receptor antagonists, it would also be of interest to determine the effects of the passive immunoneutralization of NT in the ventral mesencephalon on footshock-induced increases in the biochemically estimated activity of mesotelencephalic dopamine neurons to better understand the involvement of NT as a transducer of the effects of stress on dopamine neuronal activity. The distinct topography of conditioned versus unconditioned stress on the concentration of NT-LI in the dopamine cell body groups of the ventral mesencephalon suggests that NT may be involved in the differential activation of distinct dopamine neuronal populations by these different stressors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Nigral damage and dopaminergic hypofunction in mesencephalon-immunized guinea pigs.

To support a potential role for immune mechanisms in the destruction of substantia nigra (SN) neurons, guinea pigs were immunized with bovine mesencephalon containing SN neurons. After immunization no clinical signs of basal ganglia dysfunction appeared. However, pathological examination revealed evidence of neuronal damage in the SN in 8 of 17 guinea pigs immunized with bovine mesencephalon. No nigral pathology was noted in animals immunized with spinal cord gray matter or Freund's adjuvant alone. Accompanying the SN damage in mesencephalon-immunized guinea pigs was a 25% decrease in tyrosine hydroxylase activity in the SN and a 27% decrease in dopamine content in the striatum. Deposits of IgG were detected by immunohistochemical techniques in sections of SN from mesencephalon-immunized guinea pigs and in sections of human SN after exposure to serum from mesencephalon-immunized guinea pigs. These data document the antigenicity of SN and suggest the possibility that immune mechanisms can contribute to basal ganglia pathology.

Animals↗
PubMed1992

Tyrosine hydroxylase and acetylcholinesterase in the domestic pig mesencephalon: an immunocytochemical and histochemical study.

The mesencephalon of the young domestic pig was studied by tyrosine hydroxylase (TH) immunocytochemistry and acetylcholinesterase (AChE) histochemistry with focus on the substantia nigra (SN), the ventral tegmental area (VTA), and related areas. The purpose was to obtain information on the organization of the mesencephalic, TH immunoreactive (TH-i), and dopaminergic areas of the pig, in order to provide the necessary background for the possible use of the pig as an alternative large animal experimental model for research on Parkinson's disease, including the use of encapsulated pig dopaminergic neurons for intracerebral xenotransplantation. Significant findings in the pig, compared to observations in other species, included the presence of prominent bundles of TH-i dendrites passing in a dorsoventral direction from pars compacta into pars reticulata at middle and caudal levels of the SN, and the presence of a distinct TH-i substantia nigra pars lateralis (SNL). Caudally in the pig mesencephalon, the retrorubral field (RRF) was found to be very extensive. The view of the RRF, SN, and VTA as parts of the same integrated system was indicated by the crisscrossing of TH-i dendrites at the transitions between these areas. Estimation of the number of TH-i neurons in the SN and the VTA showed that these nuclei were of equal size in the pig. Further, it was found that TH-i nerve cells were present in the midline between the VTA in the interfascicular and rostral linear groups. TH-i nerve cells were also present in the otherwise serotoninergic dorsal raphe nuclei, just as other TH-i cells formed a perirubral cell group. AChE-positive neurons were present in both SN and VTA, and appeared to have the same size and morphology as the TH-i neurons in these areas. Within both nuclei, there were local differences in the AChE staining density, but perhaps more significantly were some marked differences in the structure of the AChE-positive neuropil of the two areas. We anticipate that the present description of the cellular organization of the TH-i dopaminergic areas in the domestic pig ventral mesencephalon will be useful for the development of a nonprimate, large animal, experimental model of Parkinson's disease.

Acetylcholinesterase↗
PubMed1992

Myelin and myelinization in the telencephalon and mesencephalon of the lizard Gallotia galloti as revealed by the immunohistochemical localization of myelin basic protein.

We have studied in the telencephalon and mesencephalon of the lizard Gallotia galloti the localization and the chronology of appearance of the immunoreactivity due to the presence of a myelin-specific protein: the Myelin Basic Protein (MBP). MBP-like immunoreactivity was present with different degrees of intensity in many nerve fibers (isolated, in tracts and in commissurae) and it was apparently more abundant in mesencephalon. During ontogeny the earliest MBP-like immunoreactivity was detected at E.36 in few tracts in mesencephalon and appeared at E.40 in telencephalon, proceeding caudo-rostrally and from the ventral (basal) to the dorsal (alar) regions. Accumulation of MBP continued after hatching. Oligodendrocyte cell bodies were not immunopositive, not even at the youngest ages studied.

Animals↗
PubMed1992

Axonal trajectories of single Forel's field H neurones in the mesencephalon, pons and medulla oblongata in the cat.

We studied axonal trajectories of single Forel's field H (FFH) neurones (n = 19) in the mesencephalon, pons and medulla by systematic antidromic threshold mapping in cats and differentiated them into two major types. Type I neurones were characterized by projections to the oculomotor nucleus (IIIn) and type II neurones by lack of projections to the IIIn. 2. Type I neurones (11/19) were further classified into three subtypes by the lowest level of projections; type Ic (n = 3) which projected to the cervical cord and type Ib (n = 7) which terminated at the ponto-medullary level and type Ia (n = 1) at more rostral level. In the mesencephalon, stem axons passed just lateral to the IIIn and projected collaterals to the IIIn and the ventral part of the periaqueductal gray matter. In the lower brain stem, stem axons of type Ib and Ic neurones passed in the dorsal part of the reticular formation or in the medial longitudinal fasciculus and projected collaterals to the dorsal part of the nucleus reticularis pontis caudalis (NRPC) and the nucleus reticularis gigantocellularis (NRG) and the reticular formation underlying the nucleus prepositus hypoglossi (PH) and the raphe region. Projections to the superior colliculus were observed in two cases. 3. Type II neurones (8/19) were classified into 2 type IIb projecting to the ponto-medullary reticular formation and 6 type IIc projecting to the cervical spinal cord. In the mesencephalon, stem axons passed through a more lateral region than those of type I and projected collaterals to the mesencephalic reticular formation and the red nucleus. In the lower brain stem, the stem axons passed in the ventral part of the reticular formation corresponding to the central tegmental tract and projected collaterals to the ventral part of the NRPC and NRG. Projections to the interstitial nucleus of Cajal, the inferior olive and the reticular formation underlying the PH were also observed. 4. The dorsal and ventral location of, respectively, stem axons of type I and type II neurones in the lower brain stem was confirmed in a larger number of neurones in experiments with restricted mapping. 5. There was not much difference in location of cell bodies of type I (totally n = 50) and type II (n = 46) neurones. The proportion of spinal-projecting neurones were larger in type II (21/46, 46%) than in type I (7/50, 14%) neurones.

Animals↗
PubMed1992

Differential expression of tyrosine hydroxylase mRNA in the developing rat mesencephalon.

1. With respect to the mesostriatal projection, the mesencephalon is composed of two dopaminergic (DA) cell populations, called dorsal tier and ventral tier. Strong evidence suggests differences in both the spatial and the temporal sequence of the innervation of the striatum between the two groups, with the ventral tier neurons innervating striatal patches prenatally and dorsal tier cells innervating striatal matrix postnatally. 2. Using in situ hybridization, we have examined the expression of the gene coding for tyrosine hydroxylase (TH) in mesencephalic DA neurons with respect to their postnatal development. Two ontogenic patterns of expression were observed: (a) dorsal tier neurons of the medial mesencephalon exhibited a sharp increase in expression beginning after birth, peaking on day 14, then decreasing and, finally, stabilizing; and (b) ventral tier neurons and dorsal tier cells from the lateral and the medial-dorsal mesencephalon showed only a slight increase in TH mRNA, reaching a plateau at P10. 3. The time course of the observed increase in TH gene expression in the first group, generally parallels the innervation of their target cells in the striatal matrix, suggesting that TH gene expression in these cells may be influenced by their postsynaptic cells or by the innervation process.

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↗
PubMed1975

5-HT-and norepinephrine-induced release of ACh from the thalamus and mesencephalon of the monkey during thermoregulation.

In the unanesthetized pigtailed monkey (Macaca nemestrina), trained to sit in a primate chair, the body temperature was monitored from the brain and colon. After an array of guide tubes had been implanted stereotaxically, isolated sits within the thalamus and mesencephalon were perfused by means of a push-pull cannula system. The perfusate was an artificial CSF containing 1.0 mug/ml of the anticholinesterase, neostigmine; each sample of effluent was assayed for the content of acetylcholine (ACh) on the eserinized guinea pig ileum. The micro-injection of 5-HT and norepinephrine into the monkey's hypothalamus in doses of 2.5-10.0 mug evoked a rise or fall in body temperature, respectively. In addition, these amines caused a concurrent change in the release of ACh at perfusion loci in both thalamus and mesencephalon. A composite anatomical mapping of the active releasing sites revealed that the output of ACh was elevated at 19 of 36 sites during the 5-HT-induced hyperthermia. The region of maximum sensitivity to 5-HT in terms of the percent change in ACh output at thalamic and mesencephalic sites was the rostral hypothalamus. These results provide further support for a neurochemical model of thermoregulation which postulates that 5-HT activates a cholinergic pathway originating in the hypothalamus which transmits the efferent signals for heat production.

Acetylcholine↗
PubMed1992

Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls.

A human genomic clone encompassing exons 1-3 of the neurotensin/neuromedin N gene was identified using a canine neurotensin complementary DNA probe. Sequence comparisons revealed that the 120-amino acid portion of the precursor sequence encoded by exons 1-3 is 89% identical to previously determined cow and dog sequences and that the proximal 250 bp of 5' flanking sequences are strikingly conserved between rat and human. The 5' flanking sequence contains cis-regulatory sites required for the induction of neurotensin/neuromedin N gene expression in PC12 cells, including AP1 sites and two cyclic adenosine-5'-monophosphate response elements. Oligonucleotide probes based on the human sequence were used to examine the distribution of neurotensin/neuromedin N messenger RNA in the ventral mesencephalon of schizophrenics and age- and sex-matched controls. Neurotensin/neuromedin N messenger RNA was observed in ventral mesencephalic cells some of which also contained melanin pigment or tyrosine hydroxylase messenger RNA. Neurons expressing neurotensin/neuromedin N messenger RNA were observed in the ventral mesencephalon of both schizophrenic and non-schizophrenic humans.

Adult↗
PubMed1976

Nuclei and tracts of the di-mesencephalon of the parakeet.

A number of nuclei and fibre systems of the parakeet di-mesencephalon, as visible in transverse series stained with the methods of HAGGQVIST and of KLUVER and BARRERA, have been described. In the preparations used, in which both neurones and myelinated fibres are visible, a relatively great number of elements can be distinguished, because of differences in cell and fibre content. Probably these elements are more sharply circumscribed than in the pigeon and therefore more readily visible. A few of them have been described for the first time, but they require experimental substantiation. Typical features of some nuclei and fibre systems of the parakeet have been pointed out. Attributing a certain type to the di-mesencephalon of the parakeet proved to be unfeasible, because of a deficient knowledge both about the elements studied and to their aspect in a sufficient number of other avian species. The pictures produced may be helpful in recognizing nuclei and fibre systems in other birds in which they are less distinct.

Animals↗
PubMed1992

A novel N18TG2 x mesencephalon cell hybrid expresses properties that suggest a dopaminergic cell line of substantia nigra origin.

A dopaminergic neuroblastoma was derived using somatic cell fusion of rat embryonic mesencephalon cells and the murine neuroblastoma-glioma cell line N18TG2. The resulting interspecies hybrid, named MES23.5, has retained a stable phenotype and karyotype for a continuous culture period of 1 year. The hybrid exhibits several properties that suggest that the parent primary neurons originated in the substantia nigra. The cell line contains tyrosine hydroxylase, which is identifiable both by biochemical and immunological methods and synthesizes dopamine, but no other catecholamine. Additionally, the cell line expresses apparent voltage-gated CA2+ channels as measured by high-affinity omega-conotoxin binding. The MES23.5 omega-conotoxin receptors are of similar affinity class to those found in adult rat mesencephalon. No dihydropyridine receptors, as measured by PN200-100 ligand binding, are present. None of these properties are found in the N18TG2 parent. At least three neuronal features, namely, tyrosine hydroxylase, dopamine synthesis, and omega-conotoxin receptor expression, are quantitatively elevated after sustained treatment with cAMP analogs. The cell line expresses a complex range of neural properties found in the dopaminergic neurons of the substantia nigra, and may therefore be useful elucidating further details of their cell biology.

Animals↗
PubMed1975

Stereotaxic coordinates for the Rhesus monkey thalamus and mesencephalon referencing visual afferents and cytoarchitecture.

When using a stereotaxic instrument for visual field stimulation we found that electrode placements in the thalamus and mesencephalon of prone rhesus monkeys with the aid of avaiable atlases showed considerable errors. As these animals are valuable for primate visual system reseach an atlas was constructed with methods that have not been used before for rhesus. In addition, the specific connections from the visual cortices, superior colliculus and retina to the thalamus and mesencephalon are also shown. Anesthetized monkeys of specific body dimensions had a matrix of pins inserted into the brain before fixation. A matrix was used so that the penetrations seen in the sectioned brain could be cross related as a control for accurate measurements of the stereotaxic planes throughout the brain. The surface of the whole brain frozen blocks were photographed on the microtome just before a cut section was taken. These calibrated pictures formed the "floor plan" of the atlas as they represent more accurately the brain geometry than individual sections which are distorted by cutting, staining and mounting. Cytoarchitectural (Nissl stain) and axonal connectional (Fink-Heimer stain) information was transferred and adjusted onto the block pictures from their corresponding stained sections. Follow up experiments showed that the present coordinates are accurate for these monkeys of restricted body dimensions. In addition, referencing visual axonal projections onto the same cytoarchitectural map in stereotaxic coordinates provides an atlas for localizing areas of the thalamus, on a basis other than cytoarchitecture, which receive combinations of visual inputs for further anatomical and physiological studies of the rhesus monkey visual system. The atlas further demonstrates that projections do not necessarily follow the cytoarchitectural definition of an area, but rather redefine the thalamus on the basis of specific axonal connections.

Animals↗
PubMed1978

Amygdaloid projections to the mesencephalon, pons and medulla oblongata in the cat.

Amygdalotegmental projections were studied in 26 cats after injections of horseradish peroxidase (HRP) in the diencephalon, midbrain and lower brain stem and in 6 cats after injection of 3H-leucine in the amygdala. Following HRP injections in the posterior hypothalamus, periaqueductal gray (PAG) and tegmentum many retrogradely labeled neurons were present in the central nucleus (CE) of the amygdala, primarily ipsilaterally. Injections of HRP in the posterior hypothalamus and mesencephalon also resulted in the labeling of neurons in the basal nucleus, pars magnocellularis. Following 3H-leucine injections in CE and adjacent structures autoradiographically labeled fibers were present in the stria terminalis and ventral amygdalofugal pathways. In the mesencephalon heavily labeled fiber bundles were located lateral to the red nucleus. Labeled fibers and terminals were distributed to the mesencephalic reticular formation, substantia nigra, ventral tegmental area and PAG. In the pontine and medullary tegmentum the bulk of passing fibers was located laterally in the reticular formation. Many labeled fibers and terminals were distributed to the parabrachial nuclei, locus coeruleus, nucleus subcoeruleus and lateral tegmental fields. Many terminals were also present in the solitary nucleus and dorsal motor nucleus of the vagus nerve. The location of the cells of origin and the distribution of the terminals of the amygdalotegmental projection suggest that this pathway plays an important role in the integration of somatic and autonomic responses associated with affective defense.

Amygdala↗
PubMed1977

Topographical distribution of acetylcholinesterase and butyrylcholinesterase in the diencephalon and mesencephalon of the garden lizard (Calotes versicolor).

The present report incorporates the histochemical mapping of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) among the various nuclei and fiber tracts of the diencephalon and mesencephalon of Calotes veriscolor. The various nuclei, for both enzymes, present varying degrees of staining, ranging from negative nuclei, on the one hand, to mild and intense staining on the other hand. Almost all of the fiber tracts reveal intense activity in BChE preparations, while they demonstrate mild and moderate activities for AChE. The nature of the various nuclei in relation to enzymatic patterns is discussed.

Acetylcholinesterase↗
PubMed1976

Convergence of the descending pathways of motor, visual and limbic cortex in the cat di- and mesencephalon.

Comparisons of the descending pathways of the motor, visual and limbic cortex in the cat revealed a number of structures in di- and mesencephalon that receive projections from all these fields. They are centrolateral (CL), paracentral (Pc), central medial (CeM) and centre median (CM), nuclei of the thalamus, zona incerta (ZI) and Forel's field H1 of the subthalamus, nucleus of the posterior commissure and anterior and posterior nuclei of the pretectum (Prt), stratum griseum intermedial and profundum of superior colliculus (CS), periaqueductal gray matter (GC) and pontine nuclei (NP). The projections from the striate field of the visual cortex to ventrobasal complex of the thalamus (VB) are shown. The results are discussed with recent data on the anatomy and physiology. A possible role of corticocortical and corticofugal fiber connections is dealt with.

Animals↗
PubMed1992

Inhibition of enkephalin metabolism and activation of mu- or delta-opioid receptors elicit opposite effects on reward and motility in the ventral mesencephalon.

The coexistence of endogenous opioid systems and dopaminergic neurones in the midbrain tegmental area suggests functional interactions between dopamine and enkephalins. Nevertheless, the identification of the specific opioid receptors associated with modulation of tegmental dopamine activity and its behavioural concomitants on motility and reward is far from clear, considering the mixed nature of the ligands usually employed. In this way, kelatorphan, a potent inhibitor of enkephalinases and selective agonists for mu- and delta-opioid receptor subtypes (DAGO and DSTBULET, respectively) were infused directly into the ventral tegmental area of the rat to study the role of endogenous enkephalins and opioid receptors in regulating spontaneous motor activity and intracranial self-stimulation behaviour. A greater increase in the rate of intracranial self-stimulation behaviour was found after activation of mu-opioid receptors in the ventral tegmental area, as compared to activation of delta-opioid receptors, whereas enhancement of endogenous enkephalins by inhibiting their metabolism through kelatorphan, reduced the rate of intracranial self-stimulation behaviour. On the contrary, spontaneous motor activity was reduced by the delta-opioid receptor agonist, whereas kelatorphan increased the movements of the animal. Taken together, these results show that inhibition of the metabolism of enkephalins in the ventral tegmental area decreased positive reinforcement from the lateral hypothalamic medial forebrain bundle and increased spontaneous movements. On the contrary, activation of both mu- or delta-opioid receptors in the ventral tegmental area significantly increased self-stimulation and decreased spontaneous motor activity, supporting the view that different mechanisms underlie the behavioural effects, resulting from enhancement of endogenous enkephalins and from activation of specific opioid receptors in the ventral mesencephalon.

Animals↗
PubMed1992

Cellular localization of tyrosine hydroxylase mRNA and cholecystokinin mRNA-containing cells in the ventral mesencephalon of the common marmoset: effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

In situ hybridization histochemistry was used to localize tyrosine hydroxylase (TH) mRNA and cholecystokinin (CCK) mRNA-expressing cells in the ventral mesencephalon of the common marmoset (Callithrix jacchus) and to examine the effects of the dopaminergic (DA) neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on these two populations of neurons in the pars compacta of the substantia nigra (SNc) and ventral tegmental area (VTA). X-ray film and liquid emulsion autoradiography of brain sections hybridized with an 35S-labelled synthetic 45-mer antisense human TH oligonucleotide probe showed strong hybridization signals and dense populations of TH mRNA expressing cells in the SNc and VTA at all levels, in the control marmoset brain. In the MPTP-treated brain, there was a substantial reduction of TH mRNA in the ventral midbrain. The loss of TH mRNA-expressing cells amounted to 98% in the lateral SNc, 88% in the medial SNc and 33% in the VTA. In situ hybridization of adjacent sections with an 35S-labelled synthetic 45-mer antisense human CCK oligonucleotide probe showed a weak hybridization signal for CCK mRNA in the ventral midbrain of the control brain. Emulsion autoradiography demonstrated CCK mRNA expressing cells in the SNc and VTA at all levels with the number of cells in the VTA similar to that for TH mRNA. However, the number of cells in the SNc expressing CCK mRNA was a fraction (1/4) of that expressing TH mRNA; moreover, the level of expression per cell was substantially less than that for TH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Early and widespread normalization of dopamine-neuropeptide Y interactions in the rat striatum after transplantation of fetal mesencephalon cells.

Graft-to-host interactions were examined at cellular level, by measuring changes in the immunoreactivity of striatal interneurons expressing neuropeptide Y after dopamine denervation and transplantation of fetal mesencephalon neurons into the striatum of adult rats. Mesencephalic cell suspensions were implanted unilaterally into the dorsal part of the striatum in rats two weeks after intranigral injection of 6-hydroxydopamine. One month and three to four months later, rats showing abolition of amphetamine-induced turning were perfused. Serial brain sections containing intrastriatal grafts were treated for tyrosine hydroxylase and neuropeptide Y immunocytochemistry, and neuropeptide Y-immunoreactive neurons were quantified in various parts of the striatal surface and compared with the striatum of controls and age-matched rats with lesions. Biochemical analyses of dopamine and dihydroxyphenyl acetic acid tissue levels and [3H]dopamine uptake were also performed on striatal samples from similar groups of normal, lesioned and transplanted rats. As early as one month post-grafting, a complete reversal of the increase in the number of neuropeptide Y-immunoreactive neurons occurring after 6-hydroxydopamine lesion was observed in dopamine-grafted animals, although a partial restoration of the tyrosine hydroxylase immunostaining and a recovery of 8% dopamine tissue level were observed in the striata of grafted as compared to normal rats. This effect on the host immunoreactivity was found to be specific to dopamine grafts, since no reversal was observed in sham-spinal cord-transplanted rats. Moreover, similar degrees of normalization were recorded either in the total striatum, or in the area immediately adjacent to the graft, or even in the zone most sensitive to dopamine denervation in terms of neuropeptide Y immunoreactivity. No more pronounced functional effects were observed three to four months after transplantation. These data suggest that grafted dopamine neurons are able to induce rapid and extensive host responsiveness, possibly by means of mechanisms involving synaptic and diffuse release of dopamine and adaptive changes in the host brain. These data may provide a cellular basis for interpreting larger behavioural recoveries than those expected to occur with dopamine grafts in view of the partial restoration of the dopaminergic innervation.

3,4-Dihydroxyphenylacetic Acid↗