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Nigral Neurons (nigral + neuron)
Selected AbstractsNeuronal activity in the subthalamic nucleus modulates the release of dopamine in the monkey striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Yasushi Shimo Abstract The primate subthalamic nucleus (STN) is commonly seen as a relay nucleus between the external and internal pallidal segments, and as an input station for cortical and thalamic information into the basal ganglia. In rodents, STN activity is also known to influence neuronal activity in the dopaminergic substantia nigra pars compacta (SNc) through inhibitory and excitatory mono- and polysynaptic pathways. Although the anatomical connections between STN and SNc are not entirely the same in primates as in rodents, the electrophysiologic and microdialysis experiments presented here show directly that this functional interaction can also be demonstrated in primates. In three Rhesus monkeys, extracellular recordings from SNc during microinjections into the STN revealed that transient pharmacologic activation of the STN by the acetylcholine receptor agonist carbachol substantially increased burst firing of single nigral neurons. Transient inactivation of the STN with microinjections of the GABA-A receptor agonist muscimol had the opposite effect. While the firing rates of individual SNc neurons changed in response to the activation or inactivation of the STN, these changes were not consistent across the entire population of SNc cells. Permanent lesions of the STN, produced in two animals with the fiber-sparing neurotoxin ibotenic acid, reduced burst firing and firing rates of SNc neurons, and substantially decreased dopamine levels in the primary recipient area of SNc projections, the striatum, as measured with microdialysis. These results suggest that activity in the primate SNc is prominently influenced by neuronal discharge in the STN, which may thus alter dopamine release in the striatum. [source] Injury induced c-Jun expression and phosphorylation in the dopaminergic nigral neurons of the rat: correlation with neuronal death and modulation by glial-cell-line-derived neurotrophic factorEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001Elisabetta Vaudano Abstract This study was designed to determine whether induction and phosphorylation of the transcription factor c-Jun is associated with lesion-induced death of dopaminergic neurons of the substantia nigra pars compacta, and if this cellular response is modulated by glial-cell-line-derived neurotrophic factor. In adult rats, delayed dopaminergic neuron cell death induced by intrastriatal 6-hydroxydopamine injection led to a marked increase in the number of both c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra pars compacta. The response was maximal before any significant loss of nigral neurons could be detected (on day 7 post lesion) and was confined to the dopaminergic neurons. Similarly, 6-hydroxydopamine lesion of the striatal dopaminergic terminals or excitotoxic lesion of the striatal target neurons in neonatal rats resulted in an increased number of c-Jun- and phosphorylated c-Jun-immunoreactive nigral nuclei that preceded the loss of nigral dopaminergic neurons. By contrast, after an excitotoxic lesion of the striatal target neurons in the adult rat, resulting in atrophy but not cell death of the nigral dopaminergic neurons, no upregulation of either c-Jun or phosphorylated c-Jun was found. A single injection of 10 µg of glial-cell-line-derived-neurotrophic factor given at day 3 after the intrastriatal 6-hydroxydopamine lesion reduced the number of c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra and protected the dopaminergic neurons from the ensuing cell death. We conclude that c-Jun induction and phosphorylation may be involved in the cellular events leading to death of nigral dopaminergic neurons in vivo and that this response can be modulated by glial-cell-line-derived-neurotrophic factor. [source] Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: Role of microgliaGLIA, Issue 1 2002Jae K. Ryu Abstract We recently showed that trisialoganglioside (GT1b) induces cell death of dopaminergic neurons in rat mesencephalic cultures (Chung et al., Neuroreport 12:611,614, 2001). The present study examines the in vivo neurotoxic effects of GT1b on dopaminergic neurons in the substantia nigra (SN) of Sprague-Dawley rats. Seven days after GT1b injection into the SN, immunocytochemical staining of SN tissue revealed death of nigral neurons, including dopaminergic neurons. Additional immunostaining using OX-42 and OX-6 antibodies showed that GT1b-activated microglia were present in the SN where degeneration of nigral neurons was found. Western blot analysis and double-labeled immunohistochemistry showed that inducible nitric oxide synthase (iNOS) was expressed in the SN, where its levels were maximal at 8 h post-GT1b injection, and that iNOS was localized exclusively within microglia. GT1b-induced loss of dopaminergic neurons in the SN was partially inhibited by NG -nitro-L-arginine methyl ester hydrochloride, an NOS inhibitor. Our results indicate that in vivo neurotoxicity of GT1b against nigral dopaminergic neurons is at least in part mediated by nitric oxide released from activated microglia. Because GT1b exists abundantly in central nervous system neuronal membranes, our data support the hypothesis that immune-mediated events triggered by endogenous compounds such as GT1b could contribute to the initiation and/or the progression of dopaminergic neuronal cell death that occurs in Parkinson's disease. GLIA 38:15,23, 2002. © 2002 Wiley-Liss, Inc. [source] Regulation of axotomy-induced dopaminergic neuron death and c-Jun phosphorylation by targeted inhibition of cdc42 or mixed lineage kinaseJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Stephen J. Crocker Abstract Mechanical transection of the nigrostriatal dopamine pathway at the medial forebrain bundle (MFB) results in the delayed degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). We have previously demonstrated that c-Jun activation is an obligate component of neuronal death in this model. Here we identified the small GTPase, cdc42, and mixed lineage kinases (MLKs) as upstream factors regulating neuronal loss and activation of c-Jun following MFB axotomy. Adenovirus-mediated expression of a dominant-negative form of cdc42 in nigral neurons blocked MFB axotomy-induced activation (phosphorylation) of MAP kinase kinase 4 (MKK4) and c-Jun, resulting in attenuation of SNpc neuronal death. Pharmacological inhibition of MLKs, MKK4-activating kinases, significantly reduced the phosphorylation of c-Jun and abrogated dopaminergic neuronal degeneration following MFB axotomy. Taken together, these findings suggest that death of nigral dopaminergic neurons following axotomy can be attenuated by targeting cell signaling events upstream of c-Jun N-terminal mitogen-activated protein kinase/c-Jun. [source] Melanized nigral neuronal numbers in Nigerian and British individualsMOVEMENT DISORDERS, Issue 8 2006Uday B. Muthane DM Abstract The role of genetic and environmental factors in etiopathogenesis of Parkinson's disease (PD) is debated. The prevalence of PD is higher among white than nonwhite populations, yet it is five times higher in nonwhites living in the United States than in Nigeria. We compare counts of melanized nigral neurons between neurologically normal Nigerians and British brains. Neuronal counts were estimated in an age-matched sample of 23 Nigerian and 7 British brains from neurologically normal individuals who had no Lewy bodies and Lewy neurites on ,-synuclein immunostaining. Two investigators blind to age and ethnicity performed counts of melanized neurons in a single 7-,m hemisections showing the substantia nigra pars compacta. No significant difference exits in the number of neurons between the Nigerian and the British subjects (P = 0.1, NS). Differences in melanized nigral neuronal numbers may not explain differences in the prevalence of PD between white and nonwhite populations, suggesting factors other than neuronal numbers contribute to differential susceptibility of black vs. white races to PD. © 2006 Movement Disorder Society [source] Neuroprotective effect of riluzole in a primate model of Parkinson's disease: Behavioral and histological evidenceMOVEMENT DISORDERS, Issue 1 2002Maria C. Obinu PhD Abstract Our study aimed to determine whether riluzole, which has shown efficacy as a disease-modifying agent in amyotrophic lateral sclerosis (ALS), is neuroprotective in a marmoset model of Parkinson's disease (PD). Reduction of energy demand by riluzole could be a rational neuroprotective strategy with good tolerability. The efficacy of riluzole was evaluated in marmosets by testing its ability to reduce MPTP-induced behavioral deficits and loss of dopaminergic nigral neurons. Marmosets were divided into two groups of four animals each: animals in Group 1 were injected twice with MPTP (2 mg/kg subcutaneous) and treated with riluzole (10 mg/kg per os b.i.d.), animals in Group 2 (controls) were injected with MPTP and with the vehicle of riluzole. A third group of marmosets which did not receive MPTP or riluzole drug was introduced for neurohistopathological studies (normal animals). Marmosets treated with riluzole preserved a better motor function and neurological performance through the 26 days of assessment when compared with the controls. Histologically, there was sparing of TH- and Nissl-stained nigral neurons and of TH-stained terminals in the striatum and the putamen in the group treated with riluzole compared to the controls. We conclude that riluzole protects dopaminergic neurons and reduces behavioral deficits in a marmoset model of PD. © 2001 Movement Disorder Society. [source] | ||||||||||