Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Liver Transcriptome Changes in Zebrafish during Acclimation to Transport-Associated Stress

Liver plays a key role during the stress acclimation, and liver transcriptome analysis of shipped zebrafish could reveal the molecular adjustments that occur in the organ. Transcriptional changes in liver were analyzed with a 44 K oligo array using total RNA from fish prior to transport and during a mock transport process - immediately after packing (0 h), at 48 and 72 h. Large numbers of genes related to a variety of biological processes and pathways were regulated, mainly during transport (at 48/72 h). Immediately after packing, transcripts of genes related to both gluconeogenesis and glycolysis were induced. During transport, induction of gluconeogenesis-linked genes and reduction of glycolysis-related genes may be supporting the increase in blood glucose levels. Inhibition of genes involved in fatty acid beta-oxidation may be pointing to the poor ability of fish to utilize energy from fatty acids, under transport conditions. Genes involved in some of the mechanisms that regulate body ammonia were also affected. Even though genes associated with certain transaminases were inhibited in liver, sustained glutamate deamination may have led to high ammonia accumulation in liver/body. Enhanced levels of gene transcripts in ubiquitination and MAPK signalling cascade and reduced levels of gene transcripts related to ROS generation via peroxisomal enzymes as well as xenobiotic metabolism may be signifying the importance of such cellular and tissue responses to maintain homeostasis. Furthermore, transcripts connected with stress and thyroid hormones were also regulated. Moreover, suppression of genes related to specific immune components may be denoting the deleterious impact of transport on fish health. Thus, this study has revealed the complex molecular -adjustments that occur in zebrafish when they are transported