Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer's Disease

Amyloid precursor protein (APP) transgenic animal models of Alzheimer's disease have become versatile tools for basic and translational research. However, there is great heterogeneity of histological, biochemical, and functional data between transgenic mouse lines, which might be due to different transgene expression patterns. Here, the expression of human APP (hAPP) by GABAergic hippocampal interneurons immunoreactive for the calcium binding proteins parvalbumin, calbindin, calretinin, and for the peptide hormone somatostatin was analyzed in Tg2576 mice by double immunofluorescent microscopy. Overall, there was no GABAergic interneuron subpopulation that did not express the transgene. On the other hand, in no case all neurons of such a subpopulation expressed hAPP. In dentate gyrus molecular layer and in stratum lacunosum moleculare less than 10% of hAPP-positive interneurons co-express any of these interneuron markers, whereas in stratum oriens hAPP-expressing neurons frequently co-express these interneuron markers to different proportions. We conclude that these neurons differentially contribute to deficits in young Tg2576 mice before the onset of Abeta plaque pathology. The detailed analysis of distinct brain region and neuron type-specific APP transgene expression patterns is indispensable to understand particular pathological features and mouse line-specific differences in neuronal and systemic functions

Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease

Amyloid precursor protein (APP) transgenic animal models of Alzheimer’s disease have become versatile tools for basic and translational research. However, there is great heterogeneity of histological, biochemical, and functional data between transgenic mouse lines, which might be due to different transgene expression patterns. Here, the expression of human APP (hAPP) by GABAergic hippocampal interneurons immunoreactive for the calcium binding proteins parvalbumin, calbindin, calretinin, and for the peptide hormone somatostatin was analyzed in Tg2576 mice by double immunofluorescent microscopy. Overall, there was no GABAergic interneuron subpopulation that did not express the transgene. On the other hand, in no case all neurons of such a subpopulation expressed hAPP. In dentate gyrus molecular layer and in stratum lacunosum moleculare less than 10% of hAPP-positive interneurons co-express any of these interneuron markers, whereas in stratum oriens hAPP-expressing neurons frequently co-express these interneuron markers to different proportions. We conclude that these neurons differentially contribute to deficits in young Tg2576 mice before the onset of Abeta plaque pathology. The detailed analysis of distinct brain region and neuron type-specific APP transgene expression patterns is indispensable to understand particular pathological features and mouse line-specific differences in neuronal and systemic functions

Analyse der neuronenspezifischen Expression des humanen Amyloidvorläuferproteins im Hippokampus von Mäusen mit Amyloid-Pathologie

Abstract nicht vorhande

Prostate cancer transcriptome compendium of long noncoding RNAs

The occurence of prostate cancer (PCa) has been consistently rising since three decades and remains the third leading cause of cancer-related deaths after lung and bowel cancer in Germany. Despite of new methods of early detection, such as prostate-specific antigen (PSA) testing, it persists to be the most common cancer in german men with over 63,400 new diagnoses in Germany every year and exhibits high prevalence in other countries of Northern andWestern Europe as well [64]. Men over the age of 70 are most commonly affected by the lethal disease, whereas an indisposition before 50 is rare. The malignant prostate tumor can be healed through operation or irradiation while the cancer hasn’t reached the stage of metastasis in which other therapeutic methods have to be employed [14] [15]. In the metastatic phase, the patient usually exhibits symptoms when the tumors size affects the urethra or the cancer spreads to other tissue, often the bones [16]. The high prevalence of this disease marks the importance of further research into prognosis and diagnosis methods, whereby identification of further biomarkers in PCa poses a major topic of scientific analysis. For this task, the effectiveness of high-throughput RNA sequencing of the transcriptome (RNA molecules of an organism or specific cell type) is frequently exploited [66]. RNA sequencing or RNA-Seq in short, offers the possibility of transcriptome assessment, enabling the identification of transcriptional aberrations in diseases as well as uncharacterized RNA species such as non-coding RNAs (ncRNAs) which remain undetected by conventional methods [49]. To alleviate interpretation of the sequenced reads they are assembled to reconstruct the transcriptome as close to the original state as possible, thus enabling rapid detection of relevant biomolecules in the data [49]. Transcriptomic studies often require highly accurate and complete gene annotations on the reference genome of the examined organism. However, most gene annotations and reference genomes are far from complete, containing a multitude of unidentified protein-coding and non-coding genes and transcripts. Therefore, refinement of reference genomes and annotations by inclusion of novel sequences, discovered in high quality transcriptome assemblies, is necessary [24]