Deutschland auf dem Weg zur Geschlechter-Gleichstellung

Die Forschungsarbeit beschäftigt sich mit der Frage, ob das Elterngeld in Deutschland (Einführung 1.1.2007) zu einer Entlastung von Frauen, d.h. einer De-Familialisierung – im Sinne einer innerfamiliären Umverteilung der unbezahlten Arbeit – beiträgt und sich Deutschland dadurch einer Geschlechter-Gleichstellung annähert. Es wird dabei die Frage gestellt, ob das Elterngeld eine Maßnahme ist, die das Verhalten von Männern innerhalb der Familie beeinflusst bzw. auch ihre Lebensverläufe ändert. Weiters ist von Interesse, ob Deutschland sein Ziel, die Väterbeteiligung mit der Einführung des Elterngeldes zu heben, auch tatsächlich erreicht hat. Der Untersuchungsgegenstand ist somit der Wohlfahrtsstaat Deutschland und insbesondere die familienpolitische Maßnahme des Elterngeldes. Der Forschungsansatz ergibt sich aus der Verbindung von Ansätzen der Wohlfahrtsstaatsforschung, der Kritik der feministischen Sozialstaatsforschung daran, sowie einer Analyse des Elterngeldes. Aus der theoretischen Auseinandersetzung ergeben sich Kategorien in Form von Fragen, anhand derer das Elterngeld konkret untersucht wird. Resümierend wird festgestellt, dass das Elterngeld aufgrund seiner einkommensabhängigen Gestaltung sowie der Einführung von Partnermonaten („Vatermonaten“) gleichstellungspolitische Akzente setzt, die von Vätern auch angenommen werden. Es erfahren demnach zumindest jene Frauen, deren Partner Elterngeld in Anspruch nehmen, eine Entlastung, d.h. sie werden de-familialisiert. Allerdings vermag das Elterngeld nicht die Problematik der unterschiedlichen Einkommensverteilung zwischen Mann und Frau aufzuheben und leistet daher auch keinen großen Beitrag zum Erreichen der Geschlechter-Gleichstellung

Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice

Single nucleotide polymorphisms (SNPs) in TMEM106B encoding the lysosomal type II transmembrane protein 106B increase the risk for frontotemporal lobar degeneration (FTLD) of GRN (progranulin gene) mutation carriers. Currently, it is unclear if progranulin (PGRN) and TMEM106B are synergistically linked and if a gain or a loss of function of TMEM106B is responsible for the increased disease risk of patients with GRN haploinsufficiency. We therefore compare behavioral abnormalities, gene expression patterns, lysosomal activity, and TDP-43 pathology in single and double knockout animals. Grn-/- /Tmem106b-/- mice show a strongly reduced life span and massive motor deficits. Gene expression analysis reveals an upregulation of molecular signature characteristic for disease-associated microglia and autophagy. Dysregulation of maturation of lysosomal proteins as well as an accumulation of ubiquitinated proteins and widespread p62 deposition suggest that proteostasis is impaired. Moreover, while single Grn-/- knockouts only occasionally show TDP-43 pathology, the double knockout mice exhibit deposition of phosphorylated TDP-43. Thus, a loss of function of TMEM106B may enhance the risk for GRN-associated FTLD by reduced protein turnover in the lysosomal/autophagic system

Early lysosomal maturation deficits in microglia triggers enhanced lysosomal activity in other brain cells of progranulin knockout mice

Background: Heterozygous loss-of-function mutations in the progranulin gene (GRN) lead to frontotemporal lobar degeneration (FTLD) while the complete loss of progranulin (PGRN) function results in neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Thus the growth factor-like protein PGRN may play an important role in lysosomal degradation. In line with a potential lysosomal function, PGRN is partially localized and processed in lysosomes. In the central nervous system (CNS), PGRN is like other lysosomal proteins highly expressed in microglia, further supporting an important role in protein degradation. We have previously reported that cathepsin (Cat) D is elevated in GRN-associated FTLD patients and Grn knockout mice. However, the primary mechanism that causes impaired protein degradation and elevated CatD levels upon PGRN deficiency in NCL and FTLD remains unclear. Methods: mRNA expression analysis of selected lysosomal hydrolases, lysosomal membrane proteins and autophagy-related genes was performed by NanoString nCounter panel. Protein expression, maturation and in vitro activity of Cat D, B and L in mouse embryonic fibroblasts (MEF) and brains of Grn knockout mice were investigated. To selectively characterize microglial and non-microglial brain cells, an acutely isolated microglia fraction using MACS microbeads (Miltenyi Biotec) conjugated with CD11b antibody and a microglia-depleted fraction were analyzed for protein expression and maturation of selected cathepsins. . Results: We demonstrate that loss of PGRN results in enhanced expression, maturation and in vitro activity of Cat D, B and L in mouse embryonic fibroblasts and brain extracts of aged Grn knockout mice. Consistent with an overall enhanced expression and activity of lysosomal proteases in brain of Grn knockout mice, we observed an age-dependent transcriptional upregulation of certain lysosomal proteases. Thus, lysosomal dysfunction is not reflected by transcriptional downregulation of lysosomal proteases but rather by the upregulation of certain lysosomal proteases in an age-dependent manner. Surprisingly, cell specific analyses identified early lysosomal deficits in microglia before enhanced cathepsin levels could be detected in other brain cells, suggesting different functional consequences on lysosomal homeostasis in microglia and other brain cells upon lack of PGRN. Conclusions: The present study uncovers early and selective lysosomal dysfunctions in Grn knockout microglia/macrophages. Dysregulated lysosomal homeostasis in microglia might trigger compensatory lysosomal changes in other brain cells

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline

Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity-specific manner in AD We measured PGRN in cerebrospinal fluid (CSF) in two of the best-characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross-sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non-carriers 10 years before the expected symptom onset. In late-onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease