di Giovanni / Di Matteo / Esposito Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra

1. Auflage 2009
ISBN: 978-3-211-92660-4
Verlag: Springer Wien
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 73, 369 Seiten, eBook

Reihe: Journal of Neural Transmission. Supplementa

This book provides a unique and timely multidisciplinary synthesis of our current knowledge of the anatomy, pharmacology, physiology and pathology of the substantia nigra pars compacta (SNc) dopaminergic neurons. The single chapters, written by top scientists in their fields, explore the life cycle of dopaminergic neurons from their birth to death, the cause of Parkinson's disease, the second most common and disabling condition in the elderly population. Nevertheless, the intracellular cascade of events leading to dopamine cell death is still unknown and, consequently, treatment is symptomatic rather than preventive. The mechanisms by which alterations cause neuronal death, new therapeutic approaches and the latest evidence of a possible de novo neurogenesis in the SNc are reviewed and singled out in different chapters. This book bridges basic science and clinical practice and will prepare the reader for the next few years, which will surely be eventful in terms of the progress of dopamine research.

Zielgruppe

Research

Autoren/Hrsg.

di Giovanni, Giuseppe

Di Matteo, Vincenzo

Esposito, Ennio

Inhaltsverzeichnis

Birth of dopaminergic neurons.- Ontogeny of Substantia Nigra Dopamine Neurons.- SNc Dopaminergic neurons.- Phenotype, Compartmental Organization and Differential Vulnerability of Nigral Dopaminergic Neurons.- Specific Vulnerability of Substantia Nigra Compacta Neurons.- The Nigrostriatal Pathway: Axonal Collateralization and Compartmental Specificity.- The Localization of Inhibitory Neurotransmitter Receptors on Dopaminergic Neurons of the Human Substantia Nigra.- Basal Ganglia Control of Substantia Nigra Dopaminergic Neurons.- Substantia Nigra Control of Basal Ganglia Nuclei.- Electrophysiological Characteristics of Dopamine Neurons: A 35-Year Update.- Chaotic Versus Stochastic Dynamics: A Critical Look at the Evidence for Nonlinear Sequence Dependent Structure in Dopamine Neurons.- Age-Dependent Changes in Dopaminergic Neuron Firing Patterns in Substantia Nigra Pars Compacta.- The Neurobiology of the Substantia Nigra Pars Compacta: from Motor to Sleep Regulation.- Non?motor Function of the Midbrain Dopaminergic Neurons.- The Substantia Nigra, the Basal Ganglia, Dopamine and Temporal Processing.- Electrophysiological and Neurochemical Characterization of 7-Nitroindazole and Molsidomine Acute and Sub-Chronic Administration Effects in the Dopaminergic Nigrostrial System in Rats.- Death of SNc Dopaminergic neurons.- Involvement of Astroglial Fibroblast Growth Factor-2 and Microglia in the Nigral 6-OHDA Parkinsonism and a Possible Role of Glucocorticoid Hormone on the Glial Mediated Local Trophism and Wound Repair.- Age and Parkinson’s Disease-Related Neuronal Death in the Substantia Nigra Pars Compacta.- Neurodegeneration in Parkinson’s Disease: Genetics Enlightens Physiopathology.- In Vivo Microdialysis in Parkinson’s Research.- Inflammatory Response inParkinsonism.- Increase of Secondary Processes of Microglial and Astroglial Cells After MPTP-Induced Degeneration in Substantia Nigra Pars Compacta of Non Human Primates.- Distinct Effects of Intranigral L-DOPA Infusion in the MPTP Rat Model of Parkinson’s Disease.- Cannabinoid CB1 Receptors are Early DownRegulated Followed by a Further UpRegulation in the Basal Ganglia of Mice with Deletion of Specific Park Genes.- Saving the SNc Dopaminergic neurons.- Neurogenesis in Substantia Nigra of Parkinsonian Brains?.- Stem Cells and Cell Replacement Therapy for Parkinson's Disease.- Gene Therapy for Parkinson’s Disease.- Immunization as Treatment for Parkinson’s Disease.- A Diet for Dopaminergic Neurons?.- Intake of Tomato-Enriched Diet Protects from 6-Hydroxydopamine-Induced Degeneration of Rat Nigral Dopaminergic Neurons.

Leseproben

Chapter 15 Involvement of Astroglial Fibroblast Growth Factor-2 and Microglia in the Nigral 6-OHDA Parkinsonism and a Possible Role of Glucocorticoid Hormone on the Glial Mediated Local Trophism and Wound Repair (p. 185)

Camila Silva, Kjell Fuxe, and Gerson Chadi

Abstract We have observed in previous studies that 6- hydroxydopamine (6-OHDA)-induced lesions in the nigrostriatal dopamine (DA) system promote increases of the astroglial basic fibroblast growth factor (FGF-2, bFGF) synthesis in the ascending DA pathways, event that could be modified by adrenosteroid hormones. Here, we first evaluated the changes of microglial reactivity in relation to the FGF-2-mediated trophic responses in the lesioned nigrostriatal DA system. 6-OHDA was injected into the left side of the rat substantia nigra. The OX42 immunohistochemistry combined with stereology showed the time course of the microglial activation. The OX42 immunoreactivity (IR) was already increased in the pars compacta of the substantia nigra (SNc) and ventral tegmental area (VTA) 2 h after the 6-OHDA injection, peaked on day 7, and remained increased on the 14th day time-interval. In the neostriatum, OX42 immunoreactive (ir) microglial profiles increased at 24 h, peaked at 72 h, was still increased at 7 days but not 14 days after the 6-OHDA injection. Two-colour immunofluorescence analysis of the tyrosine hydroxylase (TH) and OX42 IRs revealed the presence of small patches of TH IR within the activated microglia. A decreased FGF-2 IR was seen in the cytoplasm of DA neurons of the SNc and VTA as soon as 2 h after 6-OHDA injection. The majority of the DA FGF-2 ir cells of these regions had disappeared 72 h after neurotoxin. The astroglial FGF-2 IR increased in the SNc and VTA, which peaked on day 7. Two-colour immunofluorescence and immunoperoxidase analyses of the FGF-2 and OX42 IRs revealed no FGF-2 IR within the reactive or resting microglia. Second, we have evaluated in a series of biochemical experiments whether adrenocortical manipulation can interfere with the nigral lesion and the state of local astroglial reaction, looking at the TH and GFAP levels respectively. Rats were adrenalectomized (ADX) and received a nigral 6-OHDA stereotaxical injection 2 days later and sacrificed up to 3 weeks after the DA lesion.

Western blot analysis showed time-dependent decrease and elevation of TH and GFAP levels, respectively, in the lesioned versus contralateral midbrain sides, events potentiated by ADX and worsened by corticosterone replacement. ADX decreased the levels of FGF-2 protein (23 kDa isoform) in the lesioned side of the ventral midbrain compared contralaterally. The results indicate that reactive astroglia, but not reactive microglia, showed an increased FGF-2 IR in the process of DA cell degeneration induced by 6-OHDA. However, interactions between these glial cells may be relevant to the mechanisms which trigger the increased astroglial FGF-2 synthesis and thus may be related to the trophic state of DA neurons and the repair processes following DA lesion. The findings also gave further evidence that adrenocortical hormones may regulate astroglial-mediated trophic mechanisms and wound repair events in the lesioned DA system that may be relevant to the progression of Parkinson´s disease.

Keywords Parkinson • Astrocyte • Microglia • Dopamine • Fibroblast growth factor-2 • Wound repair • Neuroregeneration