Expression of Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin-3 mRNAs in Human Cortical Xenografts

Trophic factors play an important role in the development of neurons and glia. In order to study the involvement of neurotrophins in human cortical development, human fetal parietal cortical tissue, obtained after early elective abortions, was transplanted to cortical cavities in immunosuppressed rats. Using in situ hybridization it was demonstrated that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs are expressed in developing human cortical xenografts. We conclude that neurotrophins may play a role in human cortical development and rat-derived astroglial cells could be involved in establishing reciprocal “permissive sites”

Intraprenørskap i Topro Industri AS

Bacheloroppgave i Entreprenørskap fra Handelshøyskolen BI, 2018Intraprenørskap, innovasjon og omstilling er blitt ord som brukes av mange, men fylles med innhold av få. Denne oppgaven besvarer problemstillingen ”Hvordan jobber Topro Industri AS for å lykkes med intraprenørskap?” Oppgaven ser også på hvilken rolle ledelsen spiller for intraprenørskap og hvilke muligheter medarbeiderne har for å drive med intraprenørskap i Topro. Innledningsvis presentereres bakgrunn for valg av case og problemstilling. Denne delen forteller hvordan Topro startet som en attføringsbedrift og endte opp som hjørnesteinsbedrift i lokalsamfunnet, og som deretter er blitt markedsledende i sin bransje i Europa. De har nye eiere og vind i seilene. Topro er i dag i en situasjon der de må omstille hvordan de jobber med intraprenørskap fordi det går bra og de har store muligheter. Videre i oppgaven presenteres relevant teori på intraprenørskapsfeltet gjennom en modell for intraprenørskap. Vi har valgt å bruke kvalitativ metode for å kunne gå i dybden av caset og forstå produktutviklingsavdelingen som har vært i fokus i oppgaven. Kvalitative intervjuer har sammen med teorien har lagt grunnlaget for analysen og konklusjonen. Vi besvarer problemstillingen med at Topro jobber for å lykkes med intraprenørskap med fokus på prosessinnovasjon og unytting av eksisterende produkter og ressurser. De har mange av de delene som kreves for å jobbe etter en intraprenørskapsmetodikk, men har ikke satt de ulike delene sammen. Empirien viser at ledelsen og eierne ønsker å satse på innovasjon. De vil skape fremtidens rullatorer. Medarbeiderne har høy kompetanse og jobber etter intraprenørielle prinsipper i dag. Med mulighet for kontroll over verdikjeden fra produksjon til produktet leveres til kunden, er mulighetene store. Produksjonen foregår på Gjøvik, og de har riktige verktøy for prototyping og testing. For å bedre lykkes med intraprenørskap må medarbeiderne få enda mer tid til å jobbe med nye ideer, ressurser må øremerkes nye ideer og Topro må tørre å utforske mulighetene for å skape paradigmeinnovasjoner. Ledelsens viktigste oppgave er å legge til rette for dette og sørge for at ideene får en reell sjanse før de møter bedriftens immunsystem

Оценка буровых растворов применяемых для бурения продуктивных отложений в скважинах Беларуси

The assembly process of a-synuclein toward amyloid fibers is linked to neurodegeneration in Parkinson´s disease. In the present study, we capitalized on the in vitro discovery of a small-molecule accelerator of a-synuclein amyloid formation and assessed its effects when injected in brains of normal mice. An accelerator and an inhibitor of a-synuclein amyloid formation, as well as vehicle only, were injected into the striatum of normal mice and follwed by behavioral evaluation, immunohistochemistry, and metabolomics up to six months later. The effects of molecules injected into the substansia nigra of normal and a-synuclein knockout mice were also analyzed. When accelerator or inhibitor was injected into the brain of normal mice no acute compound toxicity was found. However, 6 months after single striatal injection of accelerator, mice sensorimotor functions were impaired, whereas mice injected with inhibitor had no dysfunctions. Injection of accelerator (but not inhibitor or vehicle) into the substantia nigra revealed singificant loss of tyrosine hydroxylase (TH)-positive neurons after 3 months. No loss of TH-positive neurons was found in a-synuclein knock-out mice injected with accelerator intor the substantia nigra. Metabolic serum profiles from accelerator-injected normal mice matched those of newly diagnosed Parkinson´s disease patients, whereas the profiles from inhibitor-injected normal mice matched controls. Single inoculation of a small-molecule amyloid accelerator may be a new approach for studies of early events during dopamine neurodegeneration in mice

GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function

Peer reviewe

Antioxidant-enriched diet affects early microglia accumulation and promotes regeneration of the striatal dopamine system after a 6-hydroxidopamine-induced lesion in a rat

Neuroinflammation is found both in the brain of humans suffering from Parkinson's disease and in animal models of disease. It is suggested to be involved in the pathogenesisof the disease. In the present study, in order to study the effects of antioxidants on neuroinflammation, microglial phenotypes were evaluated in rats fed with diets containing bilberries, blueberries, or crowberries at 1 and 4 weeks following striatal injection of 6-hydroxydopamine. The dopamine innervation was visualized using antibodies raised againsttyrosine hydroxlase (TH) in the striatum and in the globus pallidus. One week post-lesion, the expression of Iba1-positive cells, a general microglial marker, was significantly increased in the striatum of all animals fed with antioxidant-enriched diets compared to control-diet fed animals, while the diameter of the TH-negative zone was similar in all animals. At four weeks post-lesion, the Iba1-positive microglia was significantly reduced in animals fed with antioxidant-enriched diets. The diameter of the TH-negative zone was significantly reduced in animals fed bilberry and crowberry. The expression and distribution of ED1-positive cells was similar to that of Iba1-positive cells found in the lesionedareas. A cell division marker Ki67 revealed that few microglia were proliferating in crowberry-treated animals. Otherwise dividing cells were associated with blood capillary cells. Although the antioxidant level should be equal in the entire brain, no regeneration was found in globus pallidus, suggesting the mechanism promoting regeneration in the striatum is not effective in the globus pallidus. In conclusion, diets rich in bilberries and crowberries and with high contents of antioxidants stimulate an early phase of accumulation of reactive migroglia that fades at longer time points i.e. promotes regeneration of the striatal dopamine system

Fetal Lateral Ganglionic Eminence Attracts One of Two Morphologically Different Types of Tyrosine Hydroxylase-Positive Nerve Fibers Formed by Cultured Ventral Mesencephalon

The purpose of this study was to investigate the influence of fetal lateral ganglionic eminence (LGE) on nerve fiber outgrowth formed by fetal ventral mesencephalon (VM). Organotypic tissue cultures of fetal VM and LGE plated as single or cocultures were employed. Survival time was 3–21 days in vitro. Nerve fiber outgrowth and migration of astrocytes were analyzed using immunohistochemistry for tyrosine hydroxylase (TH) and S100. In addition, cultures were labeled with the TUNEL technique and with antibodies directed against neurofilament (NF) in order to study apoptosis and retraction of nerve fibers, respectively. The results revealed two morphologically different types of TH-positive outgrowth growing into the substrate. The initially formed TH-positive outgrowth radiated continuously without changing direction, while a second wave of TH-positive outgrowth became obvious when the initial growth already had reached a distance of approximately 1000 μm. The second wave of TH-positive outgrowth radiated from the tissue, but at a certain distance changed direction and formed a network surrounding the culture. The initially formed TH-positive growth was not associated with the presence of S100-positive astrocytes and avoided to grow into the LGE. At longer time points the first wave of TH-positive nerve fibers appeared dotted, with disrupted NF-immunoreactive fibers and in most cultures these long distance growing fibers had disappeared at 21 days in vitro. The second wave of TH-positive nerve fibers was growing onto a layer of glia and never reached the distance of the first wave. LGE became innervated by TH-positive fibers at the time point for when the second wave of TH-positive growth had been initiated, and the innervation appeared in TH-dense patches that also showed a high density of S100-positive astrocytes. Significantly increased TUNEL activity within LGE portion of cocultures was observed when TH-positive fibers entered the LGE and formed patches. In conclusion, two morphologically different types of TH-positive outgrowth were found and the initially formed fibers neither targeted the LGE nor were they guided by glial cells, but their potential to grow for long distances was high. </jats:p

Dual effects of TNFalpha on nerve fiber formation from ventral mesencephalic organotypic tissue cultures

Tumor necrosis factor alpha (TNFalpha) is toxic to dopamine neurons and increased levels of TNFalpha are observed in Parkinson's disease. Dopamine nerve fiber outgrowth in organotypic cultures of fetal ventral mesencephalon occurs in two waves. The early appearing nerve fibers are formed in the absence of astroglia, while migrating astrocytes guide the late appearing dopamine nerve fibers. TNFalpha (40 ng/ml) was added to the medium of organotypic ventral mesencephalic tissue cultures between days 4-7 and 11-14. The cultures were evaluated at days 7 or 19 to study the effects of TNFalpha on both types of nerve fiber formation. Tyrosine hydroxylase (TH)-immunohistochemistry demonstrated that the number of cultures showing non-glial-guided TH-positive outgrowth was reduced compared to controls, when TNFalpha was added at day 4. By contrast, the glial-guided TH-positive nerve fiber outgrowth and the astrocytic migration reached significantly longer distances by early TNFalpha treatment. Ki67-immunohistochemistry revealed that TNFalpha did not affect proliferation of astrocytes. Treatment with TNFalpha and antibodies against TNFalpha receptor 1 between days 4 and 7 revealed that the non-glial-guided TH-positive outgrowth reappeared. TNFalpha treatment between days 11 and 14 triggered neither the TH-positive glial-guided outgrowth, nor promoted the astrocytic migration to reach longer distances. The number of microglia was significantly increased after the late but not early TNFalpha treatment. In conclusion, TNFalpha is toxic for the non-glial dopaminergic nerve fiber outgrowth but stimulates the glial-guided outgrowth and the migration of astrocytes at an early time point. TNFalpha increased the number of microglia in VM tissue cultures after late but not after early treatment.</p