Fuxe / Agnati / Bjelke Trophic Regulation of the Basal Ganglia

Focus on Dopamine Neurons
1. Auflage 2013
ISBN: 978-1-4831-0309-9
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 627 Seiten

Trophic Regulation of the Basal Ganglia: Focus on Dopamine Neurons examines neurotransmitters. The book first discusses the role of fibroblast growth factor-2 (FGF-2) and ganglioside GM1 and the trophic regulation of the basal ganglia. Biochemical and histochemical studies on the cellular localization of FGF-2; mapping of FGF-2 and its receptors in the basal ganglia postnatally and adulthood; and mapping of the ganglioside GM1 distribution in the basal ganglia are presented. The text also explains glucocorticoid and estrogen effects on the nigrostriatal and mesolimbic dopaminergic systems; factors associated to dopaminergic cell death in Parkinson's disease; and compensatory mechanisms at dopamine D-2 receptors. The book also describes the effects of brain-derived neurotrophic factor on injured dopaminergic neurons; role of gangliosides and trophic factors in brain repair; and features of the trophic action of polyamines. The text also underscores the presence of interleukin-1 in the central nervous system; neuropeptides synthesis in astrocytes; and astrocytic kynurenines as modulators of dopaminergic function in the rat basal ganglia. The selection is a good source of information for readers wanting to study neurotransmitters.

Autoren/Hrsg.

Fuxe, K.

Agnati, L. F.

Bjelke, B.

Leseproben

1 Fibroblast Growth Factor-2, Ganglioside GM1 and the Trophic Regulation of the Basal Ganglia. Focus on the Nigrostriatal Dopamine Neurons
K. FUXE1, G. CHADI1, L.F. AGNATI2, B. TINNER1, L. ROSÉN1, A.M. JANSON1, A. MØLLER3, A. CINTRA1, Y. CAO4, M. GOLDSTEIN5, U. LINDAHL6, G. DAVID7, S.O. ÖGREN1, G. TOFFANO8, A. BAIRD9 and R.F. PETTERSSON4,     1Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden; 2Department of Human Physiology, University of Modena, Modena, Italy; 3NeuroSearch, Glostrup, Denmark; 4Ludwig Institute for Cancer Research-Stockholm Branch, Karolinska Institute, Stockholm, Sweden; 5Department of Psychiatry, New York Medical Center, NY, USA; 6Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, The Biomedical Center, Uppsala, Sweden; 7Center for Human Genetics, University of Leuven, Leuven, Belgium; 8Fidia Research Laboratories; 9Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, CA, USA Publisher Summary
This chapter describes the new morphological and functional features of fibroblast growth factor-2 (FGF-2) and gangliosides in the basal ganglia, especially in relation to the nigrostriatal dopamine system, which is degenerated in Parkinson’s disease. The mapping of FGF-2 IR demonstrates an astroglial and neuronal localization within the substantia nigra and the globus pallidus, while in the neostriatum, the FGF-2 IR is confined to the astroglial populations. In the postnatal period, all areas of the basal ganglia including substantia nigra contained neuronal but not glial FGF-2 IR. In contrast to the adult rat, also a nuclear localization of FGF-2 IR can be observed within the nerve cells. In adulthood, the nuclear localization of FGF-2 IR is not seen in most neurons with the present antiserum but mainly in the astroglial cell populations. The FGF-2 IR DA nerve cells demonstrates within the zona compacta of the substantia nigra also a codistribution with the ganglioside positive nerve terminals, with high and low affinity FGF receptors and with FGF-2 mRNA level. Introduction
Neuronotrophic factors and enhancing factors in the basal ganglia. Focus on FGF and gangliosides. Fibroblast Growth Factor-2 (FGF-2, basic FGF) is found in relatively high concentrations in the adult rat brain and exists both in low and high molecular weight forms (see book edited by Baird and Klagsbrun7). It is a potent mitogenic protein capable of acting on multiple cell types such as fibroblasts, nerve cells and glia cells and also as a potent angiogenic factor.33 A large number of brain regions including the striatum has been shown to express FGF-2 mRNA21 and FGF-1 and -2 mRNA levels have also been demonstrated within the substantia nigra of several mammals, including humans.8,13 FGF-1 IR has mainly been found to be located and expressed in neurons in sensory and motor the CNS with a sequestered localization in the perikaryon and close to the axonal nerve cell membrane.19 FGF-2 IR has been demonstrated both in neuronal and glial cell populations of the CNS8,13,31,52 with a predominant cytoplasmic IR in neurons and a predominant nuclear localization in the astroglia. It must be emphasized that FGF-2 can bind to heparan sulfate proteoglycans (HSPG) at the cell surface and in the extracellular matrix (see Bernfield and Hooper9 1991; Vlodavsky et al.,59) and therefore become sequestered within the extracellular matrix and cell surface HSPG thereby making possible a reservoir very close to the high affinity membrane FGF receptors. In view of the lack of a hydrophobic intracellular signal peptide in FGF-2 and FGF-1 it has been proposed that these factors may be released by leakage only through damaged plasma membranes.46 As gangliosides appear to strongly increase the repair processes of the central nervous system57 the cellular localization and distribution of the ganglioside GM1 in the mammalian brain has also been studied. This has been made possible by the use of immunofluorescence histochemistry of choleratoxin binding sites, the ganglioside GM1 being a receptor for choleratoxin.1,28,63 The ganglioside GM1 was found to be predominantly present within the nerve cell membrane of distinct nerve terminal networks with varying densities in the CNS including the basal ganglia, where interactions with FGF-2 may take place.1 There exists strong in vitro evidence that FGF-2 can increase survival of nerve cells and also promote neurite extension.50 The trophic effects may be both direct or indirect involving the activation of astrocytic populations.61 Also gangliosides have been shown to play a role in the functional recovery of the damaged nervous system.4,5,15 Gangliosides and in particular the ganglioside GM1 seem to play an important role in neurite growth during development. By means of double-immunolabeling procedures it has also been possible to localize FGF-1 and FGF-2 immunoreactivity to nigral and ventral tegmental dopaminergic cells.8,13 The vast majority of the mesolimbic and nigrostriatal dopaminergic cells appears to contain cytoplasmic FGF-2 immunoreactivity (IR). There exist not only substantial numbers of central nerve cell populations containing FGF-2 IR, but also large numbers of astrocyte populations, as demonstrated by double immunolabeling procedures, using GFAP immunoreactivity as a marker for astrocytes.13,31 Finally, by in situ hybridization it has also been possible to localize FGF receptor mRNA in the adult rat central nerve system with especially strong labeling of the hippocampus and of the pontine cholinergic neurons.62 Moderate labeling was observed in the substantia nigra zona compacta and the ventral tegmental area, rich in dopamine cell bodies. No labeling was observed within the nucleus caudate-putamen. A rich plexus of GM1 positive terminals exists in the zona compacta of the substantia nigra.1 In the case of mesencephalic dopamine cultures, the trophic actions of FGF-224 appear to be mediated by mesencephalic glia20,44 or at least to be dependent on the trophic factors released by astrocytes. FGF-2 has also been shown to increase the synthesis of NGF in astrocytes.66 With regard to in vivo evidence we reported in 1983 that the GM1 increases the survival of dopamine nerve cells following a unilateral partial hemitransection of the nigrostriatal dopamine system in the rat.2,57 There also exists in vivo evidence that FGF-2 and also FGF-1 may have a trophic role in the mesencephalic dopamine neurons. By the administration of FGF-2 released from gel foam implants unilaterally into the neostriatum of MPTP-treated mice, Otto and Unsicker49 were able to partially restore dopamine levels in both the implanted and non-implanted striatum. The restoration of tyrosine hydroxylase (TH) activity was also found bilaterally, while the increases in tyrosine hydroxylases immunoreactivity was only observed in the implanted striatum and close to the implant. Thus, FGF-2 partially reverse chemical and morphological deficits in the dopamine system after MPTP treatment in the ipsilateral striatum and can also produce indirect effects, leading to a compensatory activation of the nigrostriatal dopamine system also on the contralateral side. In another study, FGF-1 was stereotaxically injected into the neostriatum of MPTP-treated young mice and aging mice. Also, in this case a partial recovery or protection of TH IR nerve terminals could be found in the ipsilateral neostriatum, but only in young mice. This result illustrates the possibility that in the aging brain the FGF receptors may show deficits in their response to FGF-1.16 In the present article we will review our recent work on FGF-2 mechanisms in the basal ganglia, involving combined immunocytochemical, in situ hybridization and functional analyses, giving further evidence for neurotrophic actions of FGF-2 in vivo on the nigrostriatal DA neurons. Of major importance for this analysis has been the use of a well characterized polyclonal antiserum raised against an N-terminal (residues 1–24) synthetic peptide of bovine basic FGF-2 (1–146). This antiserum does not recognize FGF-1 (less than 1%).32 The present focus on FGF-2 and not FGF-1 is the result of a previous collaborative effort with Drs Elde, Hökfelt and Pettersson19 demonstrating prominent expression of FGF-1 in the motor and sensory neurons of the rat brain, but only weak FGF-1 immunoreactivity within the substantia nigra and the ventral tegmental area.8 Thus, at least in the rat brain, FGF-2 appears to be the more abundant of the two growth factors in DA neurons13 and thus could be of special relevance for the development of trophic treatments to be used in Parkinson’s disease. In this paper, we will also present new findings on the localization and neuroprotective activity of the...