Journal of Neural Transmission-supplement最新文献

{"title":"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.","authors":"Camila Silva,&nbsp;Kjell Fuxe,&nbsp;Gerson Chadi","doi":"10.1007/978-3-211-92660-4_15","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_15","url":null,"abstract":"<p><p>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 pro","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"185-202"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28938968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The substantia nigra, the basal ganglia, dopamine and temporal processing.","authors":"Catherine R G Jones,&nbsp;Marjan Jahanshahi","doi":"10.1007/978-3-211-92660-4_13","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_13","url":null,"abstract":"<p><p>It has been proposed that the basal ganglia are important to the temporal processing of milliseconds- and seconds-range intervals, both within the motor and perceptual domains. This review summarizes and discuses evidence from animal, pharmacological, clinical, and imaging research that supports this proposal, with particular reference to the role of the substantia nigra (SN).</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"161-71"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28939712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene therapy for Parkinson's disease.","authors":"Takao Yasuhara,&nbsp;Isao Date","doi":"10.1007/978-3-211-92660-4_25","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_25","url":null,"abstract":"<p><p>Parkinson's disease is characterized by the degeneration of the nigrostriatal dopaminergic neurons with the manifestation of tremor, rigidity, akinesia, and disturbances of postural reflexes. Medication using L-DOPA and surgeries including deep brain stimulation are the established therapies for Parkinson's disease. Cell therapies are also effective and have rapidly developed with the recent advancement in molecular biological technology including gene transfer. In this review, ex vivo gene therapy using genetically engineered cell transplantation for Parkinson's disease model of animals is described, including catecholamine/neurotrophic factor-secreting cell transplantation with or without encapsulation, as well as in vivo gene therapy using direct injection of viral vector to increase dopamine-production, ameliorate the survival of dopaminergic neurons, correct the deteriorated microenvironment, or normalize genetic abnormality. Furthermore, the future directions for clinical application are described together with recent clinical trials of gene therapy.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"301-9"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28938896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The localization of inhibitory neurotransmitter receptors on dopaminergic neurons of the human substantia nigra.","authors":"H J Waldvogel,&nbsp;K Baer,&nbsp;R L M Faull","doi":"10.1007/978-3-211-92660-4_5","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_5","url":null,"abstract":"<p><p>The substantia nigra pars compacta (SNc) is comprised mainly of dopaminergic pigmented neurons arranged in groups, with a small population of nonpigmented neurons scattered among these groups. These different types of neurons possess GABAA, GABAB, and glycine receptors. The SNc-pigmented dopaminergic neurons have postsynaptic GABAA receptors (GABAAR) with a subunit configuration containing alpha3 and gamma2 subunits, with a small population of pigmented neurons containing alpha1 beta2,3 gamma2 subunits. GABAB receptors comprised of R1 and R2 subunits and glycine receptors are also localized on pigmented neurons. In contrast, nonpigmented (mainly parvalbumin positive neurons) located in the SNc are morphologically and neurochemically similar to substantia nigra pars reticulata (SNr) neurons by showing immunoreactivity for parvalbumin and GABAARs containing immunoreactivity for alpha1, alpha3, beta2,3, and gamma2 subunits as well as GABAB R1 and R2 subunits and glycine receptors. Thus, these two neuronal types of the SNc, either pigmented dopaminergic neurons or nonpigmented parvalbumin positive neurons, have similar GABAB and glycine receptor combinations, but differ mainly in the subunit composition of the GABAARs located on their membranes. The different types of GABAARs suggest that GABAergic inputs to these neuronal types operate through GABAARs with different pharmacological and physiological profiles, whereas GABABR and glycine receptors of these cell types are likely to have similar properties.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"59-70"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28940215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory response in Parkinsonism.","authors":"Carlos Barcia,&nbsp;Francisco Ros,&nbsp;María Angeles Carrillo,&nbsp;David Aguado-Llera,&nbsp;Carmen María Ros,&nbsp;Aurora Gómez,&nbsp;Cristina Nombela,&nbsp;Vicente de Pablos,&nbsp;Emiliano Fernández-Villalba,&nbsp;Maria-Trinidad Herrero","doi":"10.1007/978-3-211-92660-4_19","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_19","url":null,"abstract":"<p><p>Inflammatory responses have been proposed as important factors in dopaminergic neuro-degeneration in Parkinsonism. Increasing evidence suggests that the alteration of the glial microenvironment induced by neuronal degeneration could be deleterious to the remaining neurons. The activation of microglia/macrophages and reactive astrocytes may have a negative effect on the surrounding parenchyma, perpetuating the neurodegenerative process. However, this alteration may also go beyond the brain parenchyma and stimulate other inflammatory changes in other systems, inducing the release of proinflammatory cytokines and probably Acute Phase Proteins (APP) and Glucocorticoids (GC). In this work we review the latest advances in the field to provide a picture of the state of the art of studies of inflammatory responses and Parkinsonism, hopefully opening up new therapeutic perspectives for patients with Parkinson's disease.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"245-52"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28938972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegeneration in Parkinson's disease: genetics enlightens physiopathology.","authors":"Olga Corti,&nbsp;Margot Fournier,&nbsp;Alexis Brice","doi":"10.1007/978-3-211-92660-4_17","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_17","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a severe neurodegenerative disorder of complex etiology and enigmatic physiopathology. In the past decade, the identification of genes involved in rare familial Parkinsonian syndromes has brought hope that understanding the functions of their products will provide insight into the molecular mechanisms responsible for neurodegeneration. The knowledge accumulated thus far has delineated two putative, potentially interconnected, disease-causing pathways: alpha-synuclein accumulation may be central to Parkinsonism due to alpha-synuclein gene defects, but possibly also to sporadic PD and other genetic forms presenting with Lewy bodies; altered mitochondrial physiology may be pivotal to Parkinsonian syndromes caused by parkin, PINK1, and possibly DJ-1 gene mutations. Adding new pieces to this fragmentary picture to determine to what extent sporadic PD and Parkinsonism due to distinct genetic causes share common pathogenic mechanisms remains a major challenge toward the development of future therapeutic strategies for these disabling disorders.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"215-21"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28938970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo microdialysis in Parkinson's research.","authors":"Giuseppe Di Giovanni,&nbsp;Ennio Esposito,&nbsp;Vincenzo Di Matteo","doi":"10.1007/978-3-211-92660-4_18","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_18","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopamine (DA) neurons in the nigrostriatal system, which in turn produces profound neurochemical changes within the basal ganglia, representing the neural substrate for parkinsonian motor symptoms. The pathogenesis of the disease is still not completely understood, but environmental and genetic factors are thought to play important roles. Research into the pathogenesis and the development of new therapeutic intervention strategies that will slow or stop the progression of the disease in human has rapidly advanced by the use of neurotoxins that specifically target DA neurons. Over the years, a broad variety of experimental models of the disease has been developed and applied in diverse animal species. The two most common toxin models used employ 6-hydroxydopamine (6-OHDA) and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenilpyridinium ion (MPTP/MPP+), either given systemically or locally applied into the nigrostriatal pathway, to resemble PD features in animals. Both neurotoxins selectively and rapidly destroy catecolaminergic neurons, although with different mechanisms. Since in vivo microdialysis coupled to high-performance liquid chromatography is an established technique for studying physiological, pharmacological, and pathological changes of a wide range of low molecular weight substances in the brain extracellular fluid, here we review the most prominent animal and human data obtained by the use of this technique in PD research.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"223-43"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28938971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substantia nigra control of basal ganglia nuclei.","authors":"Ezia Guatteo,&nbsp;Maria Letizia Cucchiaroni,&nbsp;Nicola B Mercuri","doi":"10.1007/978-3-211-92660-4_7","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_7","url":null,"abstract":"<p><p>The substantia nigra, located in the ventral mesencephalon, is one of the five nuclei that constitute the basal ganglia circuit, which controls voluntary movements. It is divided into the pars compacta and the pars reticulata, which mainly contain dopaminergic and GABAergic cells respectively. Here we overview the electrophysiological properties of these substantia nigra neurons in the pars compacta and reticulata, together with their synaptic connections, and discuss the functional effects of dopaminergic and GABAergic inputs within the basal ganglia. We also examine the phenomenon that when a deficiency of dopamine (DA) occurs (e.g. in Parkinson's disease), there is an aberrant synaptic plasticity in the basal ganglia. Moreover, we point out that the appearance of an altered pattern of neuronal firing (beta-oscillations) and synchrony among neurons in the subthalamic nucleus, the internal globus pallidus, and the substantia nigra pars reticulata has been related to motor symptoms and possibly, persistent degeneration of DA-containing neurons. Finally, we believe that, based on pathophysiological data, new and significant targets for therapeutic intervention can be identified and tested.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"91-101"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28939706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent changes in dopaminergic neuron firing patterns in substantia nigra pars compacta.","authors":"Yoshiyuki Ishida,&nbsp;Tatsuya Kozaki,&nbsp;Yoshikazu Isomura,&nbsp;Sachiko Ito,&nbsp;Ken-ichi Isobe","doi":"10.1007/978-3-211-92660-4_10","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_10","url":null,"abstract":"<p><p>Dopaminergic neurons in the substantia nigra pars compacta modulate complex motor control. Nigral dopaminergic neurons exhibit three different firing patterns in vivo: a pacemaker mode, a random mode, and a burst mode. These firing patterns are closely related to motor control. However, the changes in the proportion of the firing patterns with respect to age have not been fully established. To clarify the age-dependent changes in the proportion of dopaminergic firing patterns, we used single unit extracellular recordings in male F344/N rats. We observed that, with age, the distribution of the spikes fired by dopaminergic neurons shifts from pacemaker to random mode, and then from random to burst mode. These results suggest that the age-dependent changes in the proportion of nigral dopaminergic firing patterns may have an effect on motor function.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"129-33"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28939709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrophysiological characteristics of dopamine neurons: a 35-year update.","authors":"Wei-Xing Shi","doi":"10.1007/978-3-211-92660-4_8","DOIUrl":"https://doi.org/10.1007/978-3-211-92660-4_8","url":null,"abstract":"<p><p>This chapter consists of four sections. The first section provides a general description of the electrophysiological characteristics of dopamine (DA) neurons in both the substantia nigra and ventral tegmental area. Emphasis is placed on the differences between DA and neighboring non-DA neurons. The second section discusses the ionic mechanisms underlying the generation of action potential in DA cells. Evidence is provided to suggest that these mechanisms differ not only between DA and non-DA neurons but also between DA cells located in different areas, with different projection sites and at different developmental stages. Some of the differences may play a critical role in the vulnerability of a DA neuron to cell death. The third section describes the firing patterns of DA cells. Data are presented to show that the current \"80/160 ms\" criteria for burst identification need to be revised and that the burst firing, originally described by Bunney et al., can be described as slow oscillations in firing rate. In the ventral tegmental area, the slow oscillations are, at least partially, derived from the prefrontal cortex and part of prefrontal information is transferred to DA cells indirectly through inhibitory neurons. The final section focuses on the feedback regulation of DA cells. New evidence suggests that DA autoreceptors are coupled to multiple effectors, and both D1 and D2-like receptors are involved in long-loop feedback control of DA neurons. Because of the presence of multiple feedback and nonfeedback pathways, the effect of a drug on a DA neuron can be far more complex than an inhibition or excitation. A better understanding of the intrinsic properties of DA neurons and their regulation by afferent input will, in time, help to point to the way to more effective and safer treatments for disorders including schizophrenia, drug addiction, and Parkinson's disease.</p>","PeriodicalId":16395,"journal":{"name":"Journal of Neural Transmission-supplement","volume":" 73","pages":"103-19"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-211-92660-4_8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28939707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}