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  • 1
    Electronic Resource
    Electronic Resource
    The effect of glial cell line-derived neurotrophic factor in fibrin glue on developing dopamine neurons (1995)
    Springer
    Experimental brain research 104 (1995), S. 199-206 
    Details
    ISSN: 1432-1106
    Keywords: Fibrin glue ; Transplantation ; GDNF ; Substantia nigra ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β superfamily, promotes the survival, morphological differentiation, and high-affinity dopamine (DA) uptake of cultured nigral DA neurons. In order to test potential methodology for peptide delivery in vivo, GDNF-containing fibrin glue balls (8 μg/ball) were incorporated with pieces of fetal ventral mesencephalon (E15) and transplanted into the anterior chambers of sympathetically denervated adult rats. Five weeks after grafting, the numbers of TH-positive neurons and the nerve fiber density were significantly higher in the ventral mesencephalic grafts treated with GDNF-containing glue balls than in those treated with vehicle. In addition, the laminin and GFAP immunoreactivities were similar between the two groups. These data support the concept that GDNF is a potent trophic factor for DA neurons in vivo and suggest that fibrin glue may provide a unique and safe means to permit prolonged delivery of trophic molecules to CNS tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00242006
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  • 2
    Electronic Resource
    Electronic Resource
    Re-initiated growth from mature ventral mesencephalon: an in oculo transplant study of nigrostriatal co-grafts (1994)
    Springer
    Experimental brain research 101 (1994), S. 73-85 
    Details
    ISSN: 1432-1106
    Keywords: Substantia nigra ; Striatum ; Transplant Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 cografts 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 dopaminergc neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00243218
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  • 3
    Electronic Resource
    Electronic Resource
    Dopamine D1 Receptor-mediated Facilitation of GABAergic Neurotransmission in the Rat Strioentopeduncular Pathway and its Modulation by Adenosine A1 Receptor-mediated Mechanisms (1996)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 8 (1996), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: By using in vivo microdialysis it was found that one of the main functions of striatal dopamine D1 receptors is to selectively facilitate GABAergic neurotransmission in the ‘direct’strioentopeduncular pathway. D1 receptors localized in the entopeduncular nucleus were also found to facilitate GABA release. However, results obtained from in vivo microdialysis, in vivo electrochemistry, immunohistochemistry and confocal laser microscopy suggested that entopeduncular D1 receptors could only be activated under pharmacological conditions. Adenosine A1 receptors were found to antagonistically modulate the D1-mediated regulation of the strioentopeduncular pathway. Furthermore, using in situ hybridization D1 and A1 receptors were shown to be colocalized in medium-sized striatal neurons. These results show that the strioentopeduncular neuron is a main locus for adenosine-dopamine interactions in the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1996.tb01617.x
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  • 4
    Electronic Resource
    Electronic Resource
    Chronic Infusion of Nerve Growth Factor into Rat Striatum Increases Cholinergic Markers and Inhibits Striatal Neuronal Discharge Rate (1996)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 8 (1996), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: New strategies have recently been developed where infusion of neurotrophic factors into the brain can rescue different populations of neurons. Infusion of nerve growth factor (NGF) has been used in combination with transplants of chromaffin tissue to the striatum in the rat model of Parkinson's disease as well as to patients suffering from Alzheimer's disease. In this study we have evaluated the distribution of recombinant human NGF (rhNGF) in different brain areas and evaluated morphological and electrophysiological effects after continuous infusion for 2 weeks of rhNGF (500 μg/ml) into the striatum of normal rats. One week after termination of rhNGF infusion, NGF levels in the infused striata were 10-fold increased while in contralateral striata normal levels were found. Extracellular recordings from striatal neurons revealed a significantly decreased spontaneous firing rate (0.76 ± 0.07 Hz) in rats infused with rhNGF compared to vehicle-infused control animals (1.36 ± 0.16 Hz). Local application of rhNGF during recordings showed no direct inhibitory effect of NGF on neuronal discharge rate. Immunohistochemistry, using antibodies against acetyl cholinesterase (AChE) and glial fibrillary acidic protein (GFAP), revealed a 38.7 ± 7.0% increase in optical density of AChE immunoreactivity close to the NGF source and an increase in GFAP-positive profiles that was restricted close to the implanted dialysis fibre. In situ hybridization showed an increase in mRNAs for choline acetyltransferase, trkA, p75 and muscarinic m2 receptor in the large neurons of rhNGF-infused striatum. Messenger RNAs for m1 and m4 receptors in striatal neurons were not changed. Thus, chronic infusion of rhNGF into the striatum caused a cholinergic hyperinnervation and reduced spontaneous activity of striatal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1996.tb01326.x
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  • 5
    Electronic Resource
    Electronic Resource
    Electrophysiological and behavioural evidence for an antagonistic modulatory role of adenosine A2A receptors in dopamine D2 receptor regulation in the rat dopamine-denervated striatum (2000)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been shown that striatal adenosine A2A receptors can antagonistically interact with dopamine D2 receptors at the membrane level leading to a decrease in the affinity and efficacy of D2 receptors. Extracellular recordings and rotational behaviour were employed to obtain a correlate to these findings in an animal model of Parkinson's disease (PD). The recordings were performed in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced catecholamine depletion. While recording in the dopamine-depleted striatum, local applications of the dopamine D2 agonist quinpirole reduced neuronal activity. However, when the adenosine A2A antagonist MSX-3 was applied simultaneously with quinpirole, the inhibition of neuronal firing seen after quinpirole alone was significantly potentiated (P 〈 0.001, n = 11). In contrast, local application of CGS 21680 attenuated the effect of quinpirole. The doses of MSX-3 and CGS 21680 used to achieve the modulation of quinpirole action had no effect per se on striatal neuronal firing. Furthermore, rotational behaviour revealed that MSX-3 dose-dependently increased the number of turns when administrated together with a threshold dose of quinpirole while no enhancement was achieved when MSX-3 was combined with SKF 38393. MSX-3 alone did not induce rotational behaviour. In conclusion, this study shows that low ineffective doses of MSX-3 enhance the effect of quinpirole on striatal firing rate, while the A2A agonist exerts the opposite action. This mechanism gives a therapeutic potential to A2A antagonists in the treatment of PD by enhancing D2 receptor function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00288.x
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  • 6
    Electronic Resource
    Electronic Resource
    Voltammetric Analysis of Nigral Graft Function (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 495 (1987), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1987.tb23697.x
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  • 7
    Electronic Resource
    Electronic Resource
    Role of growth factors in degeneration and regeneration in the central nervous system; clinical experiences with NGF in Parkinson's and Alzheimer's diseases (1994)
    Springer
    Journal of neurology 242 (1994), S. S12 
    Details
    ISSN: 1432-1459
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neurotrophin-mediated mechanisms are integral to development and maintenance of the adult central nervous system. Neurotrophin expression has been shown to change rapidly in response to many different types of neuronal stress such as excitotoxic injury, mechanical lesions, epileptogenesis and ischemia. It therefore appears as if they are not only to be regarded as target-derived trophic factors in the classical sense, but also as providers of local trophic support and neuronal protection. These discoveries suggest that neurotrophins or compounds with neurotrophin-like actions might become useful in developing new treatment strategies, not only for neurodegenerative diseases, but also for other diseases and injuries to the nervous system including stroke.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00939233
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  • 8
    Electronic Resource
    Electronic Resource
    Cellular expression of GDNF mRNA suggests multiple functions inside and outside the nervous system (1996)
    Springer
    Cell & tissue research 286 (1996), S. 191-207 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Glial-cell-line-derived neurotrophic factor ; In situ hybridization ; Prenatal and postnatal development ; Basal ganglia ; Kidney ; Tooth development ; Gastrointestinal tract ; Rat (Sprague Dawley) ; Pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Glial-cell-line-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-β family and has potent neurotrophic effects on several classes of neurons including dopamine neurons and motoneurons. Here, we have used in situ hybridization to describe the development of the cellular expression of GDNF mRNA pre- and postnatally. Consistent with dopaminotrophic activity, GDNF mRNA is expressed in the developing basal ganglia and the olfactory tubercle. It is also found in a thalamic nucleus, in neurons of the substantia innominata, in the developing Purkinje neurons and the developing locus coeruleus area, and in trigeminal brainstem nuclei. In the spinal cord, neuronal expression is found in Clarke’s column. GDNF mRNA is also expressed in the dorsal horns during development. Additional GDNF mRNA expression in the head region includes the carotid body, the retina, the vibrissae, the inner ear, the ear canal, and epithelium in the nasal cavity. Prominent expression is also found in the developing teeth. The widespread expression of GDNF in developing skeletal muscle is consistent with trophic activity on α-motoneurons. The smooth muscle layers of the gastrointestinal tract are also strongly positive. A very strong signal is found in the outer mesenchyme of the developing metanephric kidney. We conclude that GDNF mRNA is expressed in many different cellular systems inside and outside the central nervous system during development, suggesting multiple functions of GDNF in the developing organism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050688
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  • 9
    Electronic Resource
    Electronic Resource
    Nerve fiber formation and catecholamine content in adult rat adrenal medullary transplants after treatment with NGF, NT-3, NT-4/5, bFGF, CNTF, and GDNF (1998)
    Springer
    Cell & tissue research 292 (1998), S. 503-512 
    Details
    ISSN: 1432-0878
    Keywords: Key words Chromaffin cells ; Trophic factors ; NGF ; NT-3 ; NT-4/5 ; CNTF ; GDNF ; bFGF ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Adrenal chromaffin cells have been characterized by the ability to change the phenotype in response to neurotrophic factor stimulation. The adrenal gland expresses numerous trophic factors endogenously, but there is still a lack of knowledge as to how the adrenal medullary cells respond to these factors. Accordingly, we evaluated nerve fiber outgrowth and cell morphology, and measured catecholamine content in adult rat adrenal medullary tissue transplanted to the anterior chamber of the eye after exposure to neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5), basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), or glial cell line-derived neurotrophic factor (GDNF) compared with the effects after exposure to recombinant human nerve growth factor (rhNGF). The results show that rhNGF was the most potent factor in inducing neurite outgrowth from the grafted chromaffin cells. CNTF was also a powerful inducer of nerve fiber formation, while NT-4/5, GDNF, and bFGF were less potent. NT-3 did not produce neurite outgrowth above that seen in vehicle-treated eyes. Combining two neurotrophins, rhNGF and NT-3, reduced nerve fiber formation. Tyrosine hydroxylase (TH) immunohistochemistry revealed good cell survival in all grafts, and no morphological differences were detected with the different treatments. The adrenaline: noradrenaline: dopamine ratio was approximately 49%: 49%: 2%, independent of treatment, and the catecholamine content was equal irrespective of treatment. In conclusion, all neurotrophic factors used, except for NT-3, promoted neurite outgrowth from adult rat chromaffin transplants. Differences in outgrowth induced by the various trophic factors did not, however, change the catecholamine content in grafts when analyzed together with the graft-derived nerve plexus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051079
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  • 10
    Electronic Resource
    Electronic Resource
    Galanin-immunoreactive nerves in the rat iris: alterations induced by denervations (1987)
    Springer
    Cell & tissue research 250 (1987), S. 267-275 
    Details
    ISSN: 1432-0878
    Keywords: Galanin ; Iris ; Choroid membrane ; Immunohistochemistry ; Trigeminal ganglion ; Superior cervical ganglion ; Calcitonin gene-related peptide ; Capsaicin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The iris and choroid membrane of the adult rat contain nerve fibers expressing immunoreactivity to the neuropeptide galanin. The density and distribution of galanin-positive nerve fibers varied from iris to iris and, particularly, among animals. Smooth, non-terminal axons were seen running in nerve bundles consisting of otherwise negative fibers. From the choroid membrane these bundles reached the iris via the ciliary body. Axons were frequently seen to branch giving rise to a sparse system of varicose, single fibers in the dilator plate and sphincter area. Galanin-positive fibers were sometimes also seen outlining blood vessels. Capsaicin, in a dose that causes permanent depletion of substance P- and cholecystokinin-immunoreactive fibers in the iris, caused no change in amount of galanin-positive fibers. Removal of the superior cervical ganglion caused a rapid and pronounced increase in the number of galanin-immunoreactive nerve fibers. Similarly, removal of the ciliary ganglion appeared to increase galanin immunoreactivity, while removal of the pterygopalatine ganglion was less effective. Lesioning of the trigeminal ganglion caused a disappearance of galanin immunoreactivity. The sympathetectomy-induced increase was counteracted by capsaicin. Galanin-positive nerve cell bodies were present in both the superior cervical and the trigeminal ganglia. In the superior cervical ganglion, immunoreactive galanin did not seem to coexist with neuropeptide Y-positive cells; in the trigeminal ganglion, some galanin-positive cells also contained calcitonin gene-related peptide (CGRP) immunoreactivity, while most cells did not. In the iris, double-staining suggested that CGRP and galanin immunoreactivities were contained in different fiber populations. We conclude that the rat iris and choroid membrane contain a sparse plexus of nerve fibers expressing galanin-like immunoreactivity. It is suggested that these fibers are derived from the trigeminal ganglion. The iris is able to respond with a pronounced increase in number of galanin-immunoreactive nerve fibers to certain denervation procedures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00219071
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