Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic parameters which are crucial for the survival of human embryonic striatal grafts need to be investigated before initiating clinical trials in Huntington's disease. In order to define the dissection of human striatal-donor tissue which gives rise to the largest amount of striatal neurons after intrastriatal transplantation, we studied the lateral and medial ganglionic eminences of embryonic striatal primordia obtained from human embryos sized 17-30 mm in crown-to-rump length (corresponding to Carnegie stages 18-23). Anatomical landmarks that demarcated the lateral and medial ganglionic eminences from each other were present only in embryos with 20 mm crown-to-rump length or larger. In monolayer cultures, the lateral ganglionic eminence gave rise to a six-fold higher yield of dopamine- and cyclic AMP-regulated phosphoprotein 32-immunoreactive striatal neurons as compared to the medial ganglionic eminence. We also xenografted the lateral and medial ganglionic eminences from five embryos sized 21-30 mm in crown-to-rump length to the ibotenate lesioned striatum of immunosuppressed rats. The grafts were evaluated with respect to general morphology, survival and integration using (immuno-) histochemical stains for acetylcholinesterase/Cresyl Violet, nicotinamide adenine dinucleotide phosphate-diaphorase, dopamine- and cyclic AMP-regulated phosphoprotein-32, tyrosine hydroxylase and calbindin-D28KD. As assessed 9-25 weeks after implantation, 13 out of 16 and 8 out of 13 grafts, in the groups grafted with the medial and lateral ganglionic eminences, respectively, had survived. Previous studies with rat donor tissue have indicated that the functional efficacy of striatal grafts is related to the development of striatal-specific P-zone regions and that these are enriched in transplants derived from the lateral as opposed to the medial ganglionic eminence. Also in the human striatal xenografts of the present study, P-zones appeared more abundant when the donor tissue was derived from the lateral ganglionic eminence. However, the proportion of graft tissue that expressed P-zone properties was always very low (at most 30%) and never approached the 80-90% previously observed in transplants of rat lateral ganglionic eminence. We conclude that the relative yield of striatal neurons in grafts of the human embryonic striatal primordium has to be improved before neural transplantation should be applied in patients with Huntington's disease.
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PMID:Phenotypic development of the human embryonic striatal primordium: a study of cultured and grafted neurons from the lateral and medial ganglionic eminences. 878 40

It has been suggested that oxidative stress plays an important role in mediating excitotoxic neuronal death. We have therefore investigated the protective effects of antioxidants against excitotoxic injury in the rat on striatal neurons both in vitro and in vivo. In the first part of the study, we determined whether two different types of antioxidants, the spin trapping agent, alpha-phenyl-tert-butyl nitrone and an inhibitor of lipid peroxidation, U-83836E, could protect cultured striatal neurons against either hypoglycemic injury or N-methyl-D-aspartate-induced excitotoxicity. Dopamine- and cyclic AMP-regulated phosphoprotein, which is enriched in medium-sized spiny neurons, was chosen as a marker for striatal neurons. alpha-Phenyl-t-butyl nitrone and U-83836E both significantly reduced cell death induced by these insults as indicated by an increased number of surviving dopamine- and cyclic AMP-regulated phospho-protein-positive neurons. The two antioxidants also promoted the survival of cultured striatal neurons grown at low cell density under serum-free culture conditions. In an in vivo experiment systemically administered alpha-phenyl-t-butyl nitrone exerted neuroprotective effects in the rat striatum following injection of the excitotoxin quinolinic acid. Apomorphine-induced rotation tests revealed that alpha-phenyl-t-butyl nitrone-treated animals were significantly less asymmetric in their motor behavior than control rats. Treatment with alpha-phenyl-t-butyl nitrone significantly reduced the size of the quinolinic acid-induced striatal lesions, as assessed by the degree of sparing of dopamine- and cyclic AMP-regulated phospho-protein-positive and nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons, and of microtubule-associated protein-2-immunorective areas. Furthermore, lesion-induced morphological changes in the substantia nigra pars reticulate, i.e. loss of dopamine- and cyclic AMP-regulated phosphoprotein-positive afferent fibers and atrophic changes due to transsynaptic degeneration, were also less extensive in the alpha-phenyl-t-butyl nitrone-treated animals. The results support the hypothesis that oxygen-free radicals contribute to excitotoxic neuronal injury. The in vivo cytoprotective effects of alpha-phenyl-t-butyl nitrone against striatal excitotoxic lesions suggest that antioxidants could be used as potential neuroprotective agents in Huntington's disease, which has been suggested to involve excitotoxicity.
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PMID:Antioxidant treatment protects striatal neurons against excitotoxic insults. 878 41

This study demonstrates that corticosterone can exacerbate the damaging effects of infused quinolinic acid (QA) on the dorsal striatum. Adult adrenalectomised male rats were pretreated subcutaneously with graded doses of corticosterone (0, 0.5, 2, 5, 20 and 40 mg/kg/day) for 2 days and then received a unilateral infusion of QA (45 nmol) (under Isoflurane/N2O anaesthesia) into the dorsal striatum. A control infusion (vehicle) was made into the striatum on the other side. Corticosterone treatment was continued and they were killed 7 days later. Plasma corticosterone was measured by radioimmunoassay, and thymus weights were used as an integrated measure of glucocorticoid activity. Lesion volumes were measured on neuronal nuclei stained sections, dopamine and cyclic AMP-regulated phosphoprotein 32 (DARRP-32) was used to assess medium spiny neurone survival, NADPH-diaphorase histochemistry to assess medium aspiny neurones and, finally, choline acetyltransferase to assess large aspiny neurones. Adrenalectomised rats showed smaller lesions than control (sham-operated) rats, suggesting significant protection. Increasing doses of corticosterone resulted in larger lesions up to an apparent ceiling effect at higher doses; there was no evidence of a U-shaped dose-response. There was a differential effect of both QA and corticosterone on the cell populations of the striatum. Medium spiny neurones were most vulnerable to the effects of QA and to the exacerbating actions of corticosterone. Medium aspiny neurones were equally vulnerable to QA but corticosterone had no additional effect. Large aspiny neurones were relatively less sensitive to QA and there was no additional action of administered corticosterone. These results show that corticosterone has a selective neuroendangering action within the striatum, but there is no evidence for a protective action of glucocorticoids at lower doses.
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PMID:Glucocorticoid enhances the neurotoxic actions of quinolinic acid in the striatum in a cell-specific manner. 1594 60