Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The irreversible mitochondrial toxin 3-nitropropionic acid (3-NPA) is a specific inhibitor of succinate dehydrogenase. We performed stereotaxic unilateral injections of 3-NPA into the nigrostriatal dopaminergic pathway in rats in order to examine its specific effects on the dopamine system. The 3-NPA-treated rats displayed unidirectional apomorphineinduced rotations, suggesting that 3-NPA selectively damages dopaminergic neurons when injected into the nigrostriatal pathway. In situ hybridization 7 weeks postinjection indicated a decrease in tyrosine hydroxylase (TH) mRNA to 30% of the noninjected side in the substantia nigra pars compacta (P < 0.05) and decreased to 62% of the noninjected side in the ventral tegmental area (VTA) (nonsignificant) of 3-NPA-lesioned rats. The number of TH mRNA positive cells showed statistically significant decreases in substantia nigra and VTA (P < 0.001) within the lesioned side. In contrast, expression of mRNAs encoding choline acetyltransferase, p75 low-affinity NGF receptor, neurotrophin tyrosine kinase receptors Trk and TrkB, and brain-derived neurotrophic factor showed neuronal sparing in several other regions of the brain. The results suggest that the nigrostriatal dopaminergic system might be selectively vulnerable to 3-NPA and demonstrate that it is possible to employ 3-NPA in a model of partial lesion of the nigrostriatal dopaminergic system resembling early stages of Parkinson's disease.
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PMID:Specific lesions in the extrapyramidal system of the rat brain induced by 3-nitropropionic acid (3-NPA). 772 Aug 19

After injury, the striatum displays several morphologic responses that may play a role in both regenerative and degenerative events. One such response is the de novo expression of the low-affinity p75 neurotrophin receptor (p75(NTR)), a gene that plays critical roles in central nervous system (CNS) cell death pathways. The present series of experiments sought to elucidate the cellular origins of this p75(NTR) response, to define the conditions under which p75(NTR) is expressed after striatal injury, and how this receptor expression is associated with neuronal plasticity. After chemical lesions, by using either the excitotoxin quinolinic acid (QA) or the complex II mitochondria inhibitor 3-nitropropionic acid (3-NP), we compared the expression of the p75(NTR) receptor within the rat striatum at different survival times. Intrastriatal administration of QA between 7 days and 21 days postlesion induced p75(NTR) expression in astrocytes that was preferentially distributed throughout the lesion core. P75(NTR) immunoreactivity within astrocytes was seen at high (100-220 nmol) but not low (50 nmol) QA doses. Seven and 21 days after 3-NP lesions, p75(NTR) expression was present in astrocytes at all doses tested (100-1,000 nmol). However, in contrast to QA, these cells were located primarily around the periphery of the lesion and not within the lesion core. At the light microscopic level p75(NTR) immunoreactive elements resembled vasculature: but did not colocalize with the pan endothelium cell marker RecA-1. In contrast, p75(NTR)-containing astrocytes colocalized with nestin, vimentin, and 5-bromo-2-deoxyuridine, indicating that these cells are newly born astrocytes. Additionally, striatal cholinergic neurons were distributed around the lesion core expressed p75(NTR) 3-5 days after lesion in both QA and 3-NP lesions. These cells did not coexpress the pro-apoptotic degradation enzyme caspase-3. Taken together, these data indicate that striatal lesions created by means of excitotoxic or metabolic mechanisms trigger the expression of p75(NTR) in structures related to progenitor cells. The expression of the p75(NTR) receptor after these chemical lesions support the concept that this receptor plays a role in the initiation of endogenous cellular events associated with CNS injury.
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PMID:Excitotoxic and metabolic damage to the rodent striatum: role of the P75 neurotrophin receptor and glial progenitors. 1189 44