Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of immortalized cell lines have been proposed to exhibit sufficient phenotypic plasticity to allow them to replace primary embryonic neurons for restorative cell transplantation. In the present experiments we evaluate the functional viability of one particular cell line, the hNT cells developed by Layton Bioscience, to replace lost neurons and alleviate asymmetrical motor deficits in a unilateral excitotoxic lesion model of Huntington's disease. Because the grafts involved implantation of human-derived cells into a rat host environment, all animals were immunosuppressed. Cyclosporin A and FK-506 were similar in providing effective immunoprotection of the hNT xenografts, and whereas the lesions induced a marked inflammatory response in the host brain, this was not exacerbated by the presence of xenograft cells. The presence of grafted cells was determined with the human-specific antigen HuNu, and good graft survival was demonstrated in almost all animals up to the longest survival examined, 16 weeks posttransplantation. Although the cells exhibited progressively greater maturation and differentiation at 10-day, 4- and 16-week time points, staining for the mature neuronal marker NeuN was at best very weak, and we were unable to detect unequivocal staining with any markers of mature striatal phenotype, including DARPP-32, calbindin, parvalbumin, choline acetyl transferase, or NADPH diaphorase (with in all cases positive control provided by good staining on the intact contralateral side of the brain). Nor were we able to detect any differences between rats with lesions alone and rats with grafts in the contralateral motor deficits exhibited in a test of skilled paw reaching or cylinder placing. These results suggest that further and more extensive studies should be undertaken to assess whether hNT neurons can show more extensive and appropriate maturation and be associated with recovery in appropriate behavioral models, before they may be considered a suitable replacement for primary embryonic cells for clinical application in Huntington's disease.
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PMID:Transplanted hNT cells ("LBS neurons") in a rat model of huntington's disease: good survival, incomplete differentiation, and limited functional recovery. 1512 58

Subpallial structures are highly conserved across the different vertebrate species. They are instrumental in the neural processing relevant to adaptive learning, decision making, motivation and behavioural strategies. Of the striatal regions, our attention has been focussed on the medial and ventral striatum (MSt), now parcellated into subregions, and also including the nucleus accumbens (Ac). Similar to mammals, the avian Ac and MSt receive glutamatergic input from the pallium and dopaminergic input from the substantia nigra and ventral tegmental area. Coincidence between glutamatergic and dopaminergic synaptic activities in the ventral/medial striatum, including the Ac, is required for memory to be formed for a given pairing of stimulus and a hedonic quality or behavioural salience. The underlying mechanism involves the activation of NMDA and dopaminergic receptors, as well as the phosphorylation of dopamine-cAMP-regulated phosphoprotein (DARPP-32). Using quantitative electron microscopy of chick specimens double-labelled against glutamate and DARPP-32 we observed direct synaptic connections between glutamate immunoreactive axon terminals and DARPP-32 labelled dendrites in the MSt and also in the posterolateral telencephalon (nidopallium caudolaterale, a prefrontal cortex equivalent region) and the hippocampus. Glutamate immunoreactive axons synapsed with both DARPP-32 immunoreactive (DARPP-32+) and DARPP-32 negative (DARPP-32-) dendrites, forming asymmetrical junctions, in all brain regions observed. The existence of direct synaptic contacts between excitatory amino acid containing axon terminals and DARPP-32 containing dopaminoceptive neurons of the chicken MSt underlines the functional homology with mammalian striatal systems.
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PMID:The organisation of the basal ganglia in the domestic chick (Gallus domesticus): anatomical localisation of DARPP-32 in relation to glutamate. 1849 30