Timed exercise stabilizes behavioral rhythms but not molecular programs in the brain's suprachiasmatic clock.

Timed daily access to a running-wheel (scheduled voluntary exercise; SVE) synchronizes rodent circadian rhythms and promotes stable, 24h rhythms in animals with genetically targeted impairment of neuropeptide signaling (Vipr2 -/- mice). Here we used RNA-seq and/or qRT-PCR to assess how this neuropeptide signaling impairment as well as SVE shapes molecular programs in the brain clock (suprachiasmatic nuclei; SCN) and peripheral tissues (liver and lung). Compared to Vipr2 +/+ animals, the SCN transcriptome of Vipr2 -/- mice showed extensive dysregulation which included core clock components, transcription factors, and neurochemicals. Furthermore, although SVE stabilized behavioral rhythms in these animals, the SCN transcriptome remained dysregulated. The molecular programs in the lung and liver of Vipr2 -/- mice were partially intact, although their response to SVE differed to that of these peripheral tissues in the Vipr2 +/+ mice. These findings highlight that SVE can correct behavioral abnormalities in circadian rhythms without causing large scale alterations to the SCN transcriptome.

Attitudes to the use of animals in biomedical research: Effects of stigma and selected research project summaries.

Three groups of participants (largely recruited from the UK) completed a survey to examine attitudes to the use of animals in biomedical research, after reading the lay (N = 182) or technical (N = 201) summary of a research project, or no summary (N = 215). They then completed a survey comprising the animal attitude (AAS), animal purpose (APQ), belief in animal mind (BAM) and empathy quotient (EQ) scales. The APQ was adapted to assess attitudes towards the use of animals for research into disorders selected to be perceived as controllable and so 'blameworthy' and potentially stigmatised (addiction and obesity) and 'psychological' (schizophrenia and addiction) versus 'physical' (cardiovascular disease and obesity), across selected species (rats, mice, fish pigs and monkeys). Thus, the APQ was used to examine how the effects of perceived controllability and the nature of the disorder affected attitudes to animal use, in different species and in the three summary groups. As expected, attitudes to animal use as measured by the AAS and the APQ (total) correlated positively with BAM and EQ scores, consistent with the assumption that the scales all measured pro-welfare attitudes. Participants in the two research summary groups did not differentiate the use of rats, mice and fish (or fish and pigs in the technical summary group), whereas all species were differentiated in the no summary group. Participants given the lay summary were as concerned about the use of animals for schizophrenia as for addiction research. APQ ratings otherwise indicated more concern for animals used for addiction research (and for obesity compared to cardiovascular disease in all summary groups). Therefore, the information provided by a research project summary influenced attitudes to use of animals in biomedical research. However, there was no overall increase in agreement with animal use in either of the summary groups.

Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes.

Hypothalamic tanycytes are neural stem and progenitor cells, but little is known of how they are regulated. Here we provide evidence that the cell adhesion molecule, NrCAM, regulates tanycytes in the adult niche. NrCAM is strongly expressed in adult mouse tanycytes. Immunohistochemical and in situ hybridization analysis revealed that NrCAM loss of function leads to both a reduced number of tanycytes and reduced expression of tanycyte-specific cell markers, along with a small reduction in tyrosine hydroxylase-positive arcuate neurons. Similar analyses of NrCAM mutants at E16 identify few changes in gene expression or cell composition, indicating that NrCAM regulates tanycytes, rather than early embryonic hypothalamic development. Neurosphere and organotypic assays support the idea that NrCAM governs cellular homeostasis. Single-cell RNA sequencing (scRNA-Seq) shows that tanycyte-specific genes, including a number that are implicated in thyroid hormone metabolism, show reduced expression in the mutant mouse. However, the mild tanycyte depletion and loss of markers observed in NrCAM-deficient mice were associated with only a subtle metabolic phenotype.