Effects of separated pair housing of female C57BL/6JRj mice on well-being

In laboratory animal facilities, it is a common code of practice to house female mice in groups. However, some experimental conditions require to house them individually, even though social isolation may impair their well-being. Therefore, we introduced a separated pair housing system and investigated whether it can refine single housing of adult female C57BL/6JRj mice. Individually ventilated cages (IVC) were divided by perforated transparent walls to separate two mice within a cage. The cage divider allowed visual, acoustic, and olfactory contact between the mice but prevented interindividual body-contact or food sharing. Short- and long-term effects of the separated pair housing system on the well-being of the mice were compared with single and group housing using a range of behavioral and physiological parameters: Nest building behavior was assessed based on the complexity of nests, the burrowing performance was measured by the amount of food pellets removed from a bottle, and trait anxiety-related behavior was tested in the free exploratory paradigm. For the evaluation of the ease of handling, interaction with the experimenter's hand was monitored. Social interaction with unknown conspecifics and locomotor activity were investigated in a test arena. Moreover, body weight and stress hormone (metabolites) were measured in feces and hair. After the mice spent a day under the respective housing conditions, concentrations of fecal corticosterone metabolites were higher in separated pair-housed mice, and they built nests of a higher complexity when compared to single-housed mice. The latter effect was still observable eight weeks later. In week 8, separated pair-housed mice showed less locomotor activity in the social interaction arena compared to mice from the other housing systems, i.e., single and group housing. Regardless of the time of testing, pair housing improved the burrowing performance. Separated pair-housed mice were more difficult to catch than group-housed mice. Hair corticosterone, progesterone, and dehydroepiandrosterone concentrations changed with increasing age independently of the housing system. There were no effects of the housing systems on trait anxiety-related behavior in the free exploratory paradigm, voluntary interaction with the experimenter's hand, and body weight. Overall, the transfer to the separated pair housing system caused short-term stress responses in female C57BL/6JRj mice. Long-term effects of separated pair housing were ambiguous. On one hand, separated pair housing increased nesting and burrowing behavior and may therefore be beneficial compared to single housing. But on the other hand, locomotor activity decreased. The study underlined that the effects of the housing conditions on physiological and behavioral parameters should be considered when analyzing and reporting animal experiments

Opposing Roles for Membrane Bound and Soluble Fas Ligand in Glaucoma-Associated Retinal Ganglion Cell Death

Glaucoma, the most frequent optic neuropathy, is a leading cause of blindness worldwide. Death of retinal ganglion cells (RGCs) occurs in all forms of glaucoma and accounts for the loss of vision, however the molecular mechanisms that cause RGC loss remain unclear. The pro-apoptotic molecule, Fas ligand, is a transmembrane protein that can be cleaved from the cell surface by metalloproteinases to release a soluble protein with antagonistic activity. Previous studies documented that constitutive ocular expression of FasL maintained immune privilege and prevented neoangeogenesis. We now show that FasL also plays a major role in retinal neurotoxicity. Importantly, in both TNFα triggered RGC death and a spontaneous model of glaucoma, gene-targeted mice that express only full-length FasL exhibit accelerated RGC death. By contrast, FasL-deficiency, or administration of soluble FasL, protected RGCs from cell death. These data identify membrane-bound FasL as a critical effector molecule and potential therapeutic target in glaucoma

Role of Fas/FasL in regulation of inflammation in vaginal tissue during HSV-2 infection

To assess the role of Fas in lesion development during genital HSV-2 infection, we used a well-established HSV-2 murine model applied to MRL-Faslpr/J (Fas−/−) and C3-Faslgld/J (FasL−/−) C57BL6 mice. In vitro infection of murine keratinocytes and epithelial cells was used to clarify molecular details of HSV-2 infection. Despite upregulation of Fas and FasL, HSV-2-infected keratinocytes and epithelial cells showed a moderate level of apoptosis due to upregulated expression of the anti-apoptotic factors Bcl-2, Akt kinase and NF-κB. Inflammatory lesions within the HSV-2-infected epithelium of C57BL6 mice consisted of infected cells upregulating Fas, FasL and Bcl-2, uninfected cells upregulating Fas and neutrophils expressing both Fas and FasL. Apoptosis was detected in HSV-2-infected cells and to even higher extent in non-infected cells surrounding HSV-2 infection sites. HSV-2 infection of Fas- and FasL-deficient mice led to increased apoptosis and stronger recruitment of neutrophils within the infection sites. We conclude that the Fas pathway participates in regulation of inflammatory response in the vaginal epithelium at the initial stage of HSV-2 infection

Sentence repetition deficits in the logopenic variant of PPA: Linguistic analysis of longitudinal and cross-sectional data

Background: The logopenic variant of primary progressive aphasia (lvPPA) is the most recently identified subtype within the primary progressive aphasia spectrum. Data characterizing this subtype based on comprehensive testing and sophisticated error analyses over time are still rare. One of the two core features of this subtype is a deficit in sentence repetition.Aims: To provide a more fine-grained linguistic characterization of the sentence repetition deficit in lvPPA.Methods & Procedures: We longitudinally analyzed sentence repetition abilities of eight lvPPA patients (mean age 67.6 years; two women) and a group of seven healthy controls (mean age 66.7 years; three women) using a novel schema for the classification of linguistic errors.Outcomes & Results: At their first examination, patients with lvPPA showed an overall impaired repetition performance compared to controls with a variable degree of impairment on the first and all subsequent dates of measurement. Two patients presented with a steady, rather unimpaired profile, similar to the control group. In progression, however, five patients showed an increase of errors especially in the categories omissions and phonological errors, occasionally resulting in violation of syntactic rules.Conclusions: These results expand existing descriptions of repetition abilities in lvPPA patients. The paper thus provides a more fine-grained classification scheme for sentence repetition performance and emphasizes the role of omissions and phonological errors in lvPPA. This, in turn, offers new insights into the linguistic nature of sentence repetition deficits in lvPPA beyond the application of mere correctness judgments