Ventral Mesencephalon

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Rolf W. Seiler - One of the best experts on this subject based on the ideXlab platform.

  • GDNF family ligands display distinct action profiles on cultured GABAergic and serotonergic neurons of rat Ventral Mesencephalon.
    Brain research, 2005
    Co-Authors: Angélique Ducray, Morten Meyer, Rolf W. Seiler, Sandra H. Krebs, Benoit Schaller, Hans R. Widmer
    Abstract:

    Glial-cell-line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN) and persephin (PSPN), known as the GDNF family ligands (GFLs), influence the development, survival and differentiation of cultured dopaminergic neurons from Ventral Mesencephalon (VM). Detailed knowledge about the effects of GFLs on other neuronal populations in the VM is essential for their potential application as therapeutic molecules for Parkinson's disease. Hence, in a comparative study, we investigated the effects of GFLs on cell densities and morphological differentiation of gamma-aminobutyric acid-immunoreactive (GABA-ir) and serotonin-ir (5-HT-ir) neurons in primary cultures of E14 rat VM. We observed that all GFLs [10 ng/ml] significantly increased GABA-ir cell densities (1.6-fold) as well as neurite length/neuron. However, only GDNF significantly increased the number of primary neurites/neuron, and none of the GFLs affected soma size of GABA-ir neurons. In contrast, only NRTN treatment significantly increased 5-HT-ir cells densities at 10 ng/ml (1.3-fold), while an augmentation was seen for GDNF and PSPN at 100 ng/ml (2.4-fold and 1.7-fold, respectively). ARTN had no effect on 5-HT-ir cell densities. Morphological analysis of 5-HT-ir neurons revealed a significant increase of soma size, number of primary neurites/neuron and neurite length/neuron after GDNF exposure, while PSPN only affected soma size, and NRTN and ARTN failed to exert any effect. In conclusion, we identified GFLs as effective neurotrophic factors for VM GABAergic and serotonergic neurons, demonstrating characteristic individual action profiles emphasizing their important and distinct roles during brain development.

  • 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
    Experimental neurology, 2001
    Co-Authors: Günter U. Höglinger, Christian Spenger, Morten Meyer, Rolf W. Seiler, H.r. Widmer, Wolfgang H. Oertel, Jürgen Sautter
    Abstract:

    Abstract 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

  • Rat fetal Ventral Mesencephalon grown as solid tissue cultures: influence of culture time and BDNF treatment on dopamine neuron survival and function
    Brain research, 1998
    Co-Authors: Günter U. Höglinger, Christian Spenger, Morten Meyer, Rolf W. Seiler, Wolfgang H. Oertel, Jürgen Sautter, Hans R. Widmer
    Abstract:

    Free-floating roller tube (FFRT) cultures of fetal rat and human nigral tissue are a means for tissue storage prior to grafting in experimental Parkinson's disease. In the present study, FFRT cultures prepared from embryonic-day-14 rat Ventral Mesencephalon were maintained for 4, 8, 12, or 16 days in vitro (DIV) in the presence or absence (controls) of BDNF [100 ng/ml]. The dopamine content in the culture medium, analyzed by HPLC, was significantly higher (4-5 fold) in the BDNF group at DIV 8 and DIV 12 compared to the corresponding control levels (40 pg/ml). The number of tyrosine hydroxylase immunoreactive neurons was significantly higher for BDNF treated cultures (2729+/-300) at DIV 8, as compared to controls (1679+/-217). At DIV 12, the culture volume was significantly increased by BDNF (1.05+/-0.12 vs. 0.71+/-0.04 mm3). Similar results were obtained for total protein. Western blot analysis demonstrated increasing signals for GFAP with increasing time in culture, but levels for control and BDNF treated cultures did not differ at any time-point investigated. In conclusion, it is suggested that the time window for effective storage of dopaminergic tissue prior to grafting can be extended by using the FFRT culture technique and that the in vitro storage may be further prolonged by treatment with BDNF.

  • Fetal Ventral Mesencephalon of human and rat origin maintained in vitro and transplanted to 6-hydroxydopamine-lesioned rats gives rise to grafts rich in dopaminergic neurons
    Experimental Brain Research, 1996
    Co-Authors: Christian Spenger, Nadia S. K. Haque, Lorenz Studer, Stephen B. Dunnett, Ljudmila Evtouchenko, Bendicht Wagner, Beatrice Bühler, Urban Lendahl, Rolf W. Seiler
    Abstract:

    Free-floating roller tube cultures of human fetal (embryonic age 6–10 weeks post-conception) and rat fetal (embryonic day 13) Ventral Mesencephalon were prepared. After 7–15 days in vitro, the mesencephalic tissue cultures were transplanted into the striatum of adult rats that had received unilateral injections of 6-hydroxydopamine into the nigrostriatal bundle 3–5 weeks prior to transplantation. Graft survival was assessed in tyrosine hydroxylase (TH)-immunostained serial sections of the grafted brains up to post-transplantation week 4 for the human fetal xenografts and post-transplantation week 11 for the rat fetal allografts. d -amphetamine-induced rotation was monitored up to 10 weeks after transplantation in the allografted animals and compared with that of lesioned-only control animals. All transplanted animals showed large, viable grafts containing TH-immunoreactive (ir) neurons. The density of TH-ir neurons in the human fetal xenografts and in rat fetal allografts was similar. A significant amelioration of the amphetamine-induced rotation was observed in the animals that received cultured tissue allografts. These results promote the feasibility of in vitro maintenance of fetal human and rat nigral tissue prior to transplantation using the free-floating roller tube technique.

  • Effects of BDNF on dopaminergic, serotonergic, and GABAergic neurons in cultures of human fetal Ventral Mesencephalon
    Experimental neurology, 1995
    Co-Authors: Christian Spencer, Carolyn Hyman, Lorenz Studer, L. Evtouchenko, Carl Jackson, Ronald M Lindsay, Mark Egli, Annette Dahl-jørgensen, Rolf W. Seiler
    Abstract:

    Abstract The neurotrophin brain-derived neurotrophic factor (BDNF) was tested for its ability to promote the survival and regulation of expression of phenotypic markers of dopaminergic, serotonergic, and GABAergic neurons in free-floating roller tube cultures of human fetal Ventral Mesencephalon. This culture system contains neurons of the anlage of the substantia nigra as well as that of the rostral raphe nucleus. Dopaminergic neuron number and tyrosine hydroxylase (TH) fiber density was monitored by TH immunocytochemistry. Measurement of dopamine (DA) content, TH enzymatic activity, serotonin (5-HT) content, and glutamic acid decarboxylase (GAD) activity were used as indices of their respective neurotransmitter function. The presence of GABAergic and serotonergic neurons in this culture system was confirmed by GABA and 5-HT immunocytochemistry. In cultures maintained in the presence of BDNF (10 ng/ml), the density of TH-positive cells was increased by 2.5-fold (P f 0.05), and the TH-positive fiber density was increased by 3.5-fold (P f 0.01), relative to control cultures. Similarly, the relative increases in DA content and TH activity were 2.6- and 2.3-fold, respectively, in the BDNF-treated cultures (P f 0.01 and P f 0.01). On a per neuron basis, DA content and TH activity were not markedly changed by BDNF treatment, suggesting that the increases in DA content and TH activity are due to more DA neurons surviving. Relative elevations were also observed in serotonin content (2.0-fold, P f 0.01) and GAD enzymatic activity (1.4-fold, P f 0.01). Future studies will need to determine whether these changes result from the direct action of BDNF on these neurons or through some indirect mechanism. The results demonstrate that BDNF has beneficial effects on cultured human fetal tissue, which may be relevant in optimizing neuronal transplantation techniques, and that multiple systems are simultaneously influenced by BDNF.

J B Becker - One of the best experts on this subject based on the ideXlab platform.

  • behavioral changes associated with grafts of embryonic Ventral Mesencephalon tissue into the striatum and or substantia nigra in a rat model of parkinson s disease
    Behavioural Brain Research, 1999
    Co-Authors: R E Johnston, J B Becker
    Abstract:

    Unilateral 6-hydroxydopamine lesion of the ascending nigrostriatal pathway in rats is a commonly used model of Parkinson's Disease. Transplantation of embryonic Ventral Mesencephalon (VM) into the striatum of such rats reduces drug-induced turning and ameliorates some simple behavioral deficits. While considerably less research has been conducted on the topic, VM grafts into the lesioned substantia nigra (SN) may induce recovery on more complex and/or spontaneous tasks. The present series of experiments was conducted to explicitly compare the behavioral efficacy of intrastriatal and intranigral VM grafts with the effects of grafts into both of these sites. Animals receiving control grafts were also tested. Following transplantation of VM or control tissue derived from E14 rat embryos, changes in drug-induced and spontaneous turning, as well as spontaneous paw use when rearing, were assessed each month for 5 months post-graft. Intrastriatal VM grafts were associated with decreases in drug-induced and spontaneous turning asymmetry but no change in paw use. Intranigral VM grafts did not affect drug-induced turning but decreased the asymmetry in spontaneous turning and spontaneous paw use. Following simultaneous VM grafts into the striatum and SN there was a decrease in drug-induced turning and an increase in the spontaneous use of the contralateral paw and both paws simultaneously. These results may have important implications for our understanding of the mechanisms mediating graft-induced behavioral recovery, both in the rat model of, and human Parkinson's Disease.

  • Behavioral changes associated with grafts of embryonic Ventral Mesencephalon tissue into the striatum and/or substantia nigra in a rat model of Parkinson's Disease.
    Behavioural brain research, 1999
    Co-Authors: R E Johnston, J B Becker
    Abstract:

    Unilateral 6-hydroxydopamine lesion of the ascending nigrostriatal pathway in rats is a commonly used model of Parkinson's Disease. Transplantation of embryonic Ventral Mesencephalon (VM) into the striatum of such rats reduces drug-induced turning and ameliorates some simple behavioral deficits. While considerably less research has been conducted on the topic, VM grafts into the lesioned substantia nigra (SN) may induce recovery on more complex and/or spontaneous tasks. The present series of experiments was conducted to explicitly compare the behavioral efficacy of intrastriatal and intranigral VM grafts with the effects of grafts into both of these sites. Animals receiving control grafts were also tested. Following transplantation of VM or control tissue derived from E14 rat embryos, changes in drug-induced and spontaneous turning, as well as spontaneous paw use when rearing, were assessed each month for 5 months post-graft. Intrastriatal VM grafts were associated with decreases in drug-induced and spontaneous turning asymmetry but no change in paw use. Intranigral VM grafts did not affect drug-induced turning but decreased the asymmetry in spontaneous turning and spontaneous paw use. Following simultaneous VM grafts into the striatum and SN there was a decrease in drug-induced turning and an increase in the spontaneous use of the contralateral paw and both paws simultaneously. These results may have important implications for our understanding of the mechanisms mediating graft-induced behavioral recovery, both in the rat model of, and human Parkinson's Disease.

A E Willing - One of the best experts on this subject based on the ideXlab platform.

  • Enhancing tyrosine hydroxylase expression and survival of fetal Ventral Mesencephalon neurons with rat or porcine Sertoli cells in vitro
    Brain research, 2006
    Co-Authors: Rania Shamekh, Jennifer D. Newcomb, Jennifer Mallery, Samuel Saporta, Don F. Cameron, Paul R. Sanberg, Joelle J. Hushen, Cyndy D. Sanberg, A E Willing
    Abstract:

    Sertoli cells (SCs) are testis-derived cells that secrete trophic factors important for the development of germ cells. Both porcine and rat SCs have been used as graft facilitators - neonatal porcine SCs to support islets in diabetes and 15-day-old rat SCs to enhance dopaminergic neuron transplants in Parkinson's disease models. However, there has never been a study examining the optimal SCs preparation to enhance tyrosine hydroxylase expression in the Ventral Mesencephalon (VM) neuron. The aim of this study was to compare the ability of both rat and porcine SCs to enhance tyrosine hydroxylase expression (TH) and neuronal survival at the same postnatal developmental ages. The SCs were isolated from 1-, 9-, or 15-day-old rat, or neonate (2-5 days), 2-month, or 4-month-old pig, and co-cultured with VM tissue from 13.5-day-old embryos. Our results showed that VM neurons co-cultured with SCs dispersed over the culture plate and had extensive neuritic outgrowth, while VM neurons cultured alone tended to cluster together forming a mass of cells with limited neurite outgrowth. TH expression was significantly increased when VM neurons were co-cultured with 15-day rat SCs or 2-month pig SCs but not when the cells were co-cultured with other ages of SCs. This suggests that secretion of trophic factors by SCs varies according to the developmental age, and it is critical for the success of graft facilitation that SCs from the appropriate age and species be used.

  • Survival of rat or mouse Ventral Mesencephalon neurons after cotransplantation with rat sertoli cells in the mouse striatum.
    Cell transplantation, 2005
    Co-Authors: Rania Shamekh, Jennifer D. Newcomb, Jennifer Mallery, Samuel Saporta, Don F. Cameron, Paul R. Sanberg, A E Willing
    Abstract:

    Transplanting cells across species (xenotransplantation) for the treatment of Parkinson's disease has been considered an option to alleviate ethical concerns and shortage of tissues. However, using this approach leads to decreased cell survival; the xenografted cells are often rejected. Sertoli cells (SCs) are testis-derived cells that provide immunological protection to developing germ cells and can enhance survival of both allografted and xenografted cells. It is not clear whether these cells will maintain their immunosuppressive support of cografted cells if they are transplanted across species. In this study, we investigated the immune modulatory capacity of SCs and the feasibility of xenografting these cells alone or with allografted and xenografted neural tissue. Transplanting xenografts of rat SCs into the mouse striatum with either rat or mouse Ventral Mesencephalon prevented astrocytic infiltration of the graft site, although all transplants showed activated microglia within the core of the graft. Surviving tyrosine hydroxylase-positive neurons were observed in all conditions, but the size of the grafts was small at best. SCs were found at 1 and 2 weeks posttransplant. However, few SCs were found at 2 months posttransplant. Further investigation is under way to characterize the immune capabilities of SCs in a xenogeneic environment.

Hans R. Widmer - One of the best experts on this subject based on the ideXlab platform.

  • Expression of Trefoil Factor 1 in the Developing and Adult Rat Ventral Mesencephalon
    2016
    Co-Authors: Pia Jensen, Michel Heimberg, Angelique D. Ducray, Hans R. Widmer, Morten Meyer
    Abstract:

    Trefoil factor 1 (TFF1) belongs to a family of secreted peptides with a characteristic tree-looped trefoil structure. TFFs are mainly expressed in the gastrointestinal tract where they play a critical role in the function of the mucosal barrier. TFF1 has been suggested as a neuropeptide, but not much is known about its expression and function in the central nervous system. We investigated the expression of TFF1 in the developing and adult rat midbrain. In the adult Ventral Mesencephalon, TFF1-immunoreactive (-ir) cells were predominantly found in the substantia nigra pars compacta (SNc), the Ventral tegmental area (VTA) and in periaqueductal areas. While around 90 % of the TFF1-ir cells in the SNc co-expressed tyrosine hydroxylase (TH), only a subpopulation of the TH-ir neurons expressed TFF1. Some TFF1-ir cells in the SNc co-expressed the calcium-binding proteins calbindin or calretinin and nearly all were NeuN-ir confirming a neuronal phenotype, which was supported by lack of co-localization with the astroglial marker glial fibrillary acidic protein (GFAP). Interestingly, at postnatal (P) day 7 and P14, a significantly higher proportion of TH-ir neurons in the SNc co-expressed TFF1 as compared to P21. In contrast, the proportion of TFF1-ir cells expressing TH remained unchanged during postnatal development. Furthermore, significantly more TH-ir neurons expressed TFF1 in the SNc, compared to the VTA at all four time-points investigated. Injection of the tracer fluorogold into the striatum of adult rats resulted in retrograde labeling of several TFF1 expressing cells in the SNc showing that

  • expression of trefoil factor 1 in the developing and adult rat Ventral Mesencephalon
    PLOS ONE, 2013
    Co-Authors: Pia Jensen, Michel Heimberg, Angelique D. Ducray, Hans R. Widmer, Morten Meyer
    Abstract:

    Trefoil factor 1 (TFF1) belongs to a family of secreted peptides with a characteristic tree-looped trefoil structure. TFFs are mainly expressed in the gastrointestinal tract where they play a critical role in the function of the mucosal barrier. TFF1 has been suggested as a neuropeptide, but not much is known about its expression and function in the central nervous system. We investigated the expression of TFF1 in the developing and adult rat midbrain. In the adult Ventral Mesencephalon, TFF1-immunoreactive (-ir) cells were predominantly found in the substantia nigra pars compacta (SNc), the Ventral tegmental area (VTA) and in periaqueductal areas. While around 90% of the TFF1-ir cells in the SNc co-expressed tyrosine hydroxylase (TH), only a subpopulation of the TH-ir neurons expressed TFF1. Some TFF1-ir cells in the SNc co-expressed the calcium-binding proteins calbindin or calretinin and nearly all were NeuN-ir confirming a neuronal phenotype, which was supported by lack of co-localization with the astroglial marker glial fibrillary acidic protein (GFAP). Interestingly, at postnatal (P) day 7 and P14, a significantly higher proportion of TH-ir neurons in the SNc co-expressed TFF1 as compared to P21. In contrast, the proportion of TFF1-ir cells expressing TH remained unchanged during postnatal development. Furthermore, significantly more TH-ir neurons expressed TFF1 in the SNc, compared to the VTA at all four time-points investigated. Injection of the tracer fluorogold into the striatum of adult rats resulted in retrograde labeling of several TFF1 expressing cells in the SNc showing that a significant fraction of the TFF1-ir cells were projection neurons. This was also reflected by unilateral loss of TFF1-ir cells in SNc of 6-hydroxylase-lesioned hemiparkinsonian rats. In conclusion, we show for the first time that distinct subpopulations of midbrain dopaminergic neurons express TFF1, and that this expression pattern is altered in a rat model of Parkinson's disease.

  • GDNF family ligands display distinct action profiles on cultured GABAergic and serotonergic neurons of rat Ventral Mesencephalon.
    Brain research, 2005
    Co-Authors: Angélique Ducray, Morten Meyer, Rolf W. Seiler, Sandra H. Krebs, Benoit Schaller, Hans R. Widmer
    Abstract:

    Glial-cell-line-derived neurotrophic factor (GDNF), neurturin (NRTN), artemin (ARTN) and persephin (PSPN), known as the GDNF family ligands (GFLs), influence the development, survival and differentiation of cultured dopaminergic neurons from Ventral Mesencephalon (VM). Detailed knowledge about the effects of GFLs on other neuronal populations in the VM is essential for their potential application as therapeutic molecules for Parkinson's disease. Hence, in a comparative study, we investigated the effects of GFLs on cell densities and morphological differentiation of gamma-aminobutyric acid-immunoreactive (GABA-ir) and serotonin-ir (5-HT-ir) neurons in primary cultures of E14 rat VM. We observed that all GFLs [10 ng/ml] significantly increased GABA-ir cell densities (1.6-fold) as well as neurite length/neuron. However, only GDNF significantly increased the number of primary neurites/neuron, and none of the GFLs affected soma size of GABA-ir neurons. In contrast, only NRTN treatment significantly increased 5-HT-ir cells densities at 10 ng/ml (1.3-fold), while an augmentation was seen for GDNF and PSPN at 100 ng/ml (2.4-fold and 1.7-fold, respectively). ARTN had no effect on 5-HT-ir cell densities. Morphological analysis of 5-HT-ir neurons revealed a significant increase of soma size, number of primary neurites/neuron and neurite length/neuron after GDNF exposure, while PSPN only affected soma size, and NRTN and ARTN failed to exert any effect. In conclusion, we identified GFLs as effective neurotrophic factors for VM GABAergic and serotonergic neurons, demonstrating characteristic individual action profiles emphasizing their important and distinct roles during brain development.

  • Rat fetal Ventral Mesencephalon grown as solid tissue cultures: influence of culture time and BDNF treatment on dopamine neuron survival and function
    Brain research, 1998
    Co-Authors: Günter U. Höglinger, Christian Spenger, Morten Meyer, Rolf W. Seiler, Wolfgang H. Oertel, Jürgen Sautter, Hans R. Widmer
    Abstract:

    Free-floating roller tube (FFRT) cultures of fetal rat and human nigral tissue are a means for tissue storage prior to grafting in experimental Parkinson's disease. In the present study, FFRT cultures prepared from embryonic-day-14 rat Ventral Mesencephalon were maintained for 4, 8, 12, or 16 days in vitro (DIV) in the presence or absence (controls) of BDNF [100 ng/ml]. The dopamine content in the culture medium, analyzed by HPLC, was significantly higher (4-5 fold) in the BDNF group at DIV 8 and DIV 12 compared to the corresponding control levels (40 pg/ml). The number of tyrosine hydroxylase immunoreactive neurons was significantly higher for BDNF treated cultures (2729+/-300) at DIV 8, as compared to controls (1679+/-217). At DIV 12, the culture volume was significantly increased by BDNF (1.05+/-0.12 vs. 0.71+/-0.04 mm3). Similar results were obtained for total protein. Western blot analysis demonstrated increasing signals for GFAP with increasing time in culture, but levels for control and BDNF treated cultures did not differ at any time-point investigated. In conclusion, it is suggested that the time window for effective storage of dopaminergic tissue prior to grafting can be extended by using the FFRT culture technique and that the in vitro storage may be further prolonged by treatment with BDNF.

P.r. Dobner - One of the best experts on this subject based on the ideXlab platform.

  • cloning of human neurotensin neuromedin n genomic sequences and expression in the Ventral Mesencephalon of schizophrenics and age sex matched controls
    Neuroscience, 1992
    Co-Authors: Andrew J. Bean, Åke Dagerlind, Tomas Hökfelt, P.r. Dobner
    Abstract:

    Abstract 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.

  • Cloning of human neurotensin/neuromedin N genomic sequences and expression in the Ventral Mesencephalon of schizophrenics and age/sex matched controls.
    Neuroscience, 1992
    Co-Authors: Andrew J. Bean, Åke Dagerlind, Tomas Hökfelt, P.r. Dobner
    Abstract:

    Abstract 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.