Biology subjects

Neumann, J.

Publications and source records attributed to Neumann, J..

21 records · Page 2Linked to original sources

bioRxiv2019

CRISPR-Cas9 generated Pompe knock-in murine model exhibits early-onset cardiomyopathy and impaired skeletal muscle function

Infantile-onset Pompe Disease (IOPD), caused by mutations in lysosomal acid alpha-glucosidase (Gaa), manifests rapidly progressive fatal cardiac and skeletal myopathy incompletely attenuated by synthetic GAA intravenous infusions. The currently available murine model does not fully simulate human IOPD, displaying skeletal myopathy with late-onset hypertrophic cardiomyopathy. Bearing a Cre-LoxP induced exonic disruption of the murine Gaa gene, this model is also not amenable to genome-editing based therapeutic approaches. We report the early onset of severe hypertrophic cardiomyopathy in a novel murine IOPD model generated utilizing CRISPR-Cas9 homology-directed recombination to harbor the orthologous Gaa mutation c.1826dupA (p.Y609*), which causes human IOPD. We demonstrate the dual sgRNA approach with a single-stranded oligonucleotide donor is highly specific for the Gaac.1826 locus without genomic off-target effects or rearrangements. Cardiac and skeletal muscle were deficient in Gaa mRNA and enzymatic activity and accumulated high levels of glycogen. The mice demonstrated skeletal muscle weakness but did not experience early mortality. Altogether, these results demonstrate that the CRISPR-Cas9 generated Gaac.1826dupA murine model recapitulates hypertrophic cardiomyopathy and skeletal muscle weakness of human IOPD, indicating its utility for evaluation of novel therapeutics.

molecular biology↗

bioRxiv2019

Activity in the left amygdala in response to foods differs depending on the emotional context

Emotions can influence our eating behaviors. Facing an acute stressor or being in a positive mood are examples of situations that tend to modify appetite. However, the question of how the brain integrates these emotion-related changes in food processing remains elusive. Here we designed an emotional priming fMRI task to test if amygdala activity during food pictures differs depending on the emotional context. Fifty-eight female participants completed a novel emotional priming task, in which emotional images of negative, neutral or positive situations were followed by pictures of either foods or objects. After priming in each trial, participants rated how much they liked the shown foods or objects. We analyzed how brain activity during the contrast \"foods > objects\" changed according to the emotional context - in the whole brain and in the amygdala. We also examined the potential effect of adiposity (i.e., waist circumference). We observed a higher difference between liking scores for foods and objects after positive priming than after neutral priming. In the left amygdala, activity in the contrast \"foods > objects\" was higher after neutral priming relative to negative priming. Waist circumference was not significantly related to this emotional priming effect on food processing. Our results suggest that emotional context alters food and non-food perception, both in terms of liking scores and with regards to engagement of the left amygdala. Moreover, our findings indicate that emotional context has an impact on the salience advantage of food, possibly affecting eating behavior.

neuroscience↗

bioRxiv2019

Hemispheric asymmetries in resting-state EEG and fMRI are related to approach and avoidance behaviour, but not to eating behaviour or BMI

Much of our behaviour is driven by two motivational dimensions - approach and avoidance. These have been related to frontal hemispheric asymmetries in clinical and resting-state EEG studies: approach was linked to higher activity of the left relative to the right hemisphere, while avoidance was related to the opposite pattern. Increased approach behaviour, specifically towards unhealthy foods, is also observed in obesity and has been linked to asymmetry in the framework of the right-brain hypothesis of obesity. Here, we aimed to replicate previous EEG findings of hemispheric asymmetries for self-reported approach/avoidance behaviour and to relate them to eating behaviour. Further, we assessed whether resting fMRI hemispheric asymmetries can be detected and whether they are related to approach/avoidance, eating behaviour, and BMI. We analysed 3 samples: Sample 1 (n=117) containing EEG and fMRI data from lean participants, and Samples 2 (n=89) and 3 (n=152) containing fMRI data from lean, overweight, and obese participants. While in Sample 1 approach in women was related to EEG and fMRI hemispheric asymmetries, in Samples 2 and 3 this effect was not significant. Here, hemispheric asymmetries were neither related to BMI nor eating behaviour. Our study partly replicates previous EEG findings regarding hemispheric asymmetries and indicates that this relationship could also be captured using fMRI. Our findings suggest that eating behaviour and obesity are likely to be mediated by mechanisms not directly relating to frontal asymmetries in neuronal activation quantified with EEG and fMRI.

neuroscience↗