Pluripotent stem cells (PSCSCs) are defined by their potential to generate all cell types of an organism. The standard assay for pluripotency of mouse PSCSCs is cell transmission through the germline, but for human PSCSCs researchers depend on indirect methods such as differentiation into teratomas in immunodeficient mice. Here we report PluriTest, a robust open-access bioinformatic assay of pluripotency in human cells based on their gene expression profiles
Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.
Corticotropin releasing factor in concentrations of 15 to 250 nanomoles per liter increased the spontaneous discharge frequency and decreased the size of hyperpolarizations after burst discharges in CA1 and CA3 pyramidal neurons of rat hippocampal slices. Concentrations greater than 250 nanomoles per liter also depolarized the cells. These excitatory actions of corticotropin releasing factor may involve a novel calcium-dependent process.
A critical role in place learning has been attributed to place cells within the cornu ammonis 1 (CA1) sector of the hippocampus in rodents. The role of CA1 cells in the human hippocampus with regard to place learning remains elusive. Using a virtual Morris water maze, we investigated patients with acute transient global amnesia (TGA), a rare self-limiting dysfunction of the hippocampal system. Fourteen individuals with selective and focal lesions in the CA1 sector of the hippocampus showed a profound impairment in place learning. The size of the lesions and the duration of the TGA correlated with the deficit in the performance.
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