710 research outputs found

    Modulation of brain polyphosphoinositide metabolism by acth and beta-endorphin:structure-activity studies

    Get PDF
    This study describes effects of ACTH1–24 and β-endorphin on brain polyphosphoinositide metabolism in vitro. The interconversion of these polyanionic phospholipids was studied by incubation of a lysed synaptosomal fraction with [γ-32P]ATP. Of the membrane phospholipids only PA, DPI and TPI became labeled. The reference peptide ACTH1–24 stimulated the formation of TPI and inhibited the production of PA. For effects on TPI formation both the sequences ACTH5–7 and ACTH10–16 were needed. Effects of PA formation required the sequences ACTH7–10 and ACTH10–16. The basic amino acids in ACTH10–16 seemed to be of crucial importance for the peptide effects. A stimulatory effect on DPI was visible when ACTH was shortened from the N-terminus, and the essential information was in ACTH7–10. β-endorphin inhibited PA formation and this effect was abolished by C-terminal shortening to γ-endorphin. Other fragments of the C-terminus of β-LPH, including the enkephalins, were ineffective. It is concluded that the structure-activity relationship obtTPI/PA formation correlates with a similar relationship obtained on excessive grooming behavior in vivo. A possible correlation between the effects on polyPI metabolism and opiate-like effects, and effects on extinction of active avoidance behavior in vivo is discussed

    Ex vivo adenoviral vector-mediated neurotrophin gene transfer to olfactory ensheathing glia: Effects on rubrospinal tract regeneration, lesion size, and functional recovery after implantation in the injured rat spinal cord

    Get PDF
    The present study uniquely combines olfactory ensheathing glia (OEG) implantation with ex vivo adenoviral (AdV) vector-based neurotrophin gene therapy in an attempt to enhance regeneration after cervical spinal cord injury. Primary OEG were transduced with AdV vectors encoding rat brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or bacterial marker protein -galactosidase (LacZ) and subsequently implanted into adult Fischer rats directly after unilateral transection of the dorsolateral funiculus. Implanted animals received a total of 2 x 105 OEG that were subjected to transduction with neurotrophin-encoding AdV vector, AdV-LacZ, or no vector, respectively. At 4 months after injury, lesion volumes were smaller in all OEG implanted rats and significantly reduced in size after implantation of neurotrophin-encoding AdV vector-transduced OEG. All OEG grafts were filled with neurofilament-positive axons, and AdV vector-mediated expression of BDNF by implanted cells significantly enhanced regenerative sprouting of the rubrospinal tract. Behavioral analysis revealed that OEG-implanted rats displayed better locomotion during horizontal rope walking than unimplanted lesioned controls. Recovery of hind limb function was also improved after implantation of OEG that were transduced with a BDNF- or NT-3-encoding AdV vector. Hind limb performance during horizontal rope locomotion did directly correlate with lesion size, suggesting that neuroprotective effects of OEG implants contributed to the level of functional recovery. Thus, our results demonstrate that genetic engineering of OEG not only resulted in a cell that was more effective in promoting axonal outgrowth but could also lead to enhanced recovery after injury, possibly by sparing of spinal tissue
    • …
    corecore