Biomedical subjects

Thorleif Thorlin

Publications and source records attributed to Thorleif Thorlin.

4 recordsLinked to original sources

PubMed2003

Opioid-induced proliferation through the MAPK pathway in cultures of adult hippocampal progenitors.

Administration of opioid agonists or antagonists has been reported to regulate proliferation or survival of neural progenitors in vivo. Here we report that beta-endorphin and selective mu-opioid receptor (MOR) and delta-opioid receptor (DOR) agonists stimulate proliferation of isolated rat adult hippocampal progenitors (AHPs). The AHPs were found to express DORs and MORs, but not kappa-opioid receptors. Incubation with beta-endorphin for 48 h increased the number of AHPs found in mitosis, the total DNA content, and the expression of proliferating cell nuclear antigen. This proliferative effect from beta-endorphin on AHPs was antagonized by naloxone. The beta-endorphin-induced proliferation was mediated through phosphorylation of extracellular signal-regulated kinases 1 and 2 and dependent on phosphatidylinositol 3-kinase and both intra- and extracellular calcium. These data suggest a role for the opioid system in the regulation of proliferation in progenitors from the adult hippocampus.

Animals↗

PubMed2003

Mu- and delta-opioid receptor antagonists decrease proliferation and increase neurogenesis in cultures of rat adult hippocampal progenitors.

Opioids have previously been shown to affect proliferation and differentiation in various neural cell types. In the present study, cultured rat adult hippocampal progenitors (AHPs) were shown to release beta-endorphin. Membrane preparations of AHPs were found to bind [125I]beta-endorphin, and immunoreactivity for mu- and delta-opioid receptors (MORs and DORs), but not for kappa-opioid receptors (KORs), was found on cells in culture. Both DNA content and [3H]thymidine incorporation were reduced after a 48-h incubation with 100 microM naloxone, 10 micro m naltrindole or 10 microM beta-funaltrexamine, but not nor-binaltorphimine, suggesting proliferative actions of endogenous opioids against MORs and DORs on AHPs. Furthermore, analysis of gene and protein expression after incubation with MOR and DOR antagonists for 48 h using RT-PCR and Western blotting suggested decreased signalling through the mitogen-activated protein kinase (MAPK) pathway and lowered levels of genes and proteins that are important in cell cycling. Cultures were incubated with naloxone (10 or 100 microM) for 10 days to study the effects on differentiation. This resulted in an approximately threefold increase in neurogenesis, a threefold decrease in astrogliogenesis and a 50% decrease in oligodendrogenesis. In conclusion, this study suggests that reduced signalling through MORs and DORs decreases proliferation in rat AHPs, increases the number of in vitro-generated neurons and reduces the number of astrocytes and oligodendrocytes in culture.

Animals↗

PubMed2003

Computation of electric and magnetic stimulation in human head using the 3-D impedance method.

A comparative, computational study of the modeling of transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) is presented using a human head model. The magnetic fields from a typical TMS coil of figure-eight type is modeled using the Biot-Savart law. The TMS coil is placed in a position used clinically for treatment of depression. Induced current densities and electric field distributions are calculated in the model using the impedance method. The calculations are made using driving currents and wave forms typical in the clinical setting. The obtained results are compared and contrasted with the corresponding ECT results. In the ECT case, a uniform current density is injected on one side of the head and extracted from the equal area on the opposite side of the head. The area of the injected currents corresponds to the electrode placement used in the clinic. The currents and electric fields, thus, produced within the model are computed using the same three-dimensional impedance method as used for the TMS case. The ECT calculations are made using currents and wave forms typical in the clinic. The electrical tissue properties are obtained from a 4-Cole-Cole model. The numerical results obtained are shown on a two-dimenaional cross section of the model. In this study, we find that the current densities and electric fields in the ECT case are stronger and deeper penetrating than the corresponding TMS quantities but both methods show biologically interesting current levels deep inside the brain.

Adult↗

PubMed2002

Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning.

A pharmacological screen identified the H+ and K+ ATPase transporter as obligatory for normal orientation of the left-right body axis in Xenopus. Maternal H+/K+-ATPase mRNA is symmetrically expressed in the 1-cell Xenopus embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H+/K+-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H+/K+-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H+/K+-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H+/K+-ATPase activity.

2-Pyridinylmethylsulfinylbenzimidazoles↗