Mouse Hepatitis Virus Infection Upregulates Genes Involved in Innate Immune Responses

Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, the time of peak inflammation, reveals robust expression of IFN-γ, IL-12 and mKC. Data suggest that activated microglia and inflammatory mediators contribute to a local CNS microenvironment that regulates viral replication and IFN-γ production during the acute phase of infection, which in turn can cause phagolysosome maturation and phagocytosis of the myelin sheath, leading to demyelination.     

Behavioral and Neural Correlates of Executive Functioning in Musicians and Non-Musicians

Executive functions (EF) are cognitive capacities that allow for planned, controlled behavior and strongly correlate with academic abilities. Several extracurricular activities have been shown to improve EF, however, the relationship between musical training and EF remains unclear due to methodological limitations in previous studies. To explore this further, two experiments were performed; one with 30 adults with and without musical training and one with 27 musically trained and untrained children (matched for general cognitive abilities and socioeconomic variables) with a standardized EF battery. Furthermore, the neural correlates of EF skills in musically trained and untrained children were investigated using fMRI. Adult musicians compared to non-musicians showed enhanced performance on measures of cognitive flexibility, working memory, and verbal fluency. Musically trained children showed enhanced performance on measures of verbal fluency and processing speed, and significantly greater activation in pre-SMA/SMA and right VLPFC during rule representation and task-switching compared to musically untrained children. Overall, musicians show enhanced performance on several constructs of EF, and musically trained children further show heightened brain activation in traditional EF regions during task-switching. These results support the working hypothesis that musical training may promote the development and maintenance of certain EF skills, which could mediate the previously reported links between musical training and enhanced cognitive skills and academic achievement.     

Effects of Modified Handling on the Physiological Stress of Trawled-and-Discarded Yellowfin Bream (Acanthopagrus australis)

Modified handling is often claimed to reduce (sub-)lethal impacts among organisms caught-and-released in fisheries. Improving welfare of discarded fish warrants investigation, when their survival is of both economic and ecological importance. In this study, juvenile yellowfin bream (Acanthopagrus australis) were trawled in an Australian penaeid fishery and then discarded after on-board sorting in either dry or water-filled (modified) trays and with delays in starting sorting of either 2 or 15 mins. Blood plasma cortisol, glucose and potassium were sampled immediately from some yellowfin bream, while others were placed into cages (with controls) and sampled after five days. Irrespective of their on-board handling, all trawled fish incurred a relatively high acute stress response (i.e. an increase in Mean ± SE cortisol from a baseline of <4 to 122.0 ± 14.9 ng/mL) that was mostly attributed to the trawling process, and exacerbated by variation in key parameters (low salinity, changes in water temperature and the presence of jellyfish Catostylus mosaicus in catches). When C. mosaicus was present, the potassium concentrations of fish sampled immediately after sorting were significantly elevated, possibly due to nematocyst contact and subsequent inhibition of ion pumps or cytolysis. Stress also increased during handling in response to warmer air temperatures and longer exposure. While most fish had substantially recovered by 120 hours after discarding, deploying selective trawls (to reduce jellyfish) for short periods and then quickly sorting catches in water would benefit discard welfare.     

In a Model of Batten Disease,Palmitoyl Protein Thioesterase-1 Deficiency Is Associated with Brown Adipose Tissue and Thermoregulation Abnormalities

Infantile neuronal ceroid lipofuscinosis (INCL) is a fatal neurodegenerative disorder caused by a deficiency of palmitoyl-protein thioesterase-1 (PPT1). We have previously shown that children with INCL have increased risk of hypothermia during anesthesia and that PPT1-deficiency in mice is associated with disruption of adaptive energy metabolism, downregulation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and mitochondrial dysfunction. Here we hypothesized that Ppt1-knockout mice, a well-studied model of INCL that shows many of the neurologic manifestations of the disease, would recapitulate the thermoregulation impairment observed in children with INCL. We also hypothesized that when exposed to cold, Ppt1-knockout mice would be unable to maintain body temperature as in mice thermogenesis requires upregulation of Pgc-1α and uncoupling protein 1 (Ucp-1) in brown adipose tissue. We found that the Ppt1-KO mice had lower basal body temperature as they aged and developed hypothermia during cold exposure. Surprisingly, this inability to maintain body temperature during cold exposure in Ppt1-KO mice was associated with an adequate upregulation of Pgc-1α and Ucp-1 but with lower levels of sympathetic neurotransmitters in brown adipose tissue. In addition, during baseline conditions, brown adipose tissue of Ppt1-KO mice had less vacuolization (lipid droplets) compared to wild-type animals. After cold stress, wild-type animals had significant decreases whereas Ppt1-KO had insignificant changes in lipid droplets compared with baseline measurements, thus suggesting that Ppt1-KO had less lipolysis in response to cold stress. These results uncover a previously unknown phenotype associated with PPT1 deficiency, that of altered thermoregulation, which is associated with impaired lipolysis and neurotransmitter release to brown adipose tissue during cold exposure. These findings suggest that INCL should be added to the list of neurodegenerative diseases that are linked to alterations in peripheral metabolic processes. In addition, extrapolating these findings clinically, impaired thermoregulation and hypothermia are potential risks in patients with INCL.