Biology subjects

Urs, N.

Publications and source records attributed to Urs, N..

4 recordsLinked to original sources

bioRxiv2026

Semaglutide promotes intramuscular fat formation after injury

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become defining therapies in the management of type 2 diabetes and obesity. Despite recent interest in the effects of GLP-1RA therapy on skeletal muscle, their influence on muscle repair after injury remains largely untested. Because GLP-1RA use is common in populations at heightened risk for diminished regenerative capacity, a critical unanswered question is whether GLP-1R agonism supports muscle regeneration or alters the normal course of recovery after injury. Using intramuscular glycerol injection as an adipogenic injury model, we assessed whether semaglutide, a widely prescribed GLP-1RA, alters the balance between myogenesis and adipogenesis during regeneration. Surprisingly, semaglutide treatment markedly increased the formation of intramuscular adipose tissue (IMAT) and inhibited the growth of regenerated fibers. These effects were injury-dependent, as uninjured muscle showed no detectable differences in IMAT or myofiber size. Together, these findings identify a previously underappreciated context in which GLP-1RA therapy may adversely affect muscle quality.

developmental biology↗

bioRxiv2022

Labeled lines for fat and sugar reward combine to promote overeating

Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits are poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for detection of dietary fats and sugars. Using activity-dependent genetic capture of nutrient-specific vagal neurons activated in response gut infusions, we demonstrate the existence of separate hard-wired reward circuits for fat and sugar that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases overeating compared to fat or sugar alone. This work provides new insight on the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.

neuroscience↗

bioRxiv2017

Mapping nonapoptotic caspase activity with a transgenic reporter in mice

The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity in rodent brains. We therefore generated a transgenic mouse expressing a highly sensitive and specific fluorescent reporter of caspase activity, with peak signal localized to the nucleus. As a proof of concept, we first obtained evidence that nonapoptotic caspase activity influences neurophysiology in an amygdalar circuit. Then focusing on the amygdala, we were able to quantify a sex-specific persistent elevation in caspase activity in females after restraint stress. This simple in vivo caspase activity reporter will facilitate systems-level studies of apoptotic and nonapoptotic phenomena in behavioral and pathological models. Significance StatementCaspase-3 is an enzyme that can cause cell death when highly active but can also perform important cellular functions, such as maturation and structural changes, when only weakly or transiently active. Despite the importance of this nonlethal type of caspase activity, there is no straightforward method to measure it in live rodents. We therefore developed mice that have a fluorescent reporter that is sensitive enough to detect nonlethal caspase activity. Surprisingly, we found that weak caspase activity influences the synchrony of neuronal firing across different brain regions. We also observed increased caspase activity in female mice after severe stress. This simple caspase activity reporter can subserve multiple applications in behavior and pathology research.

neuroscience↗

bioRxiv2017

Increased Activity of Tyrosine Hydroxylase Leads to Elevated Amphetamine Response and Markers of Oxidative Stress in Transgenic Mice

In Parkinsons disease, noradrenergic cells of the locus coeruleus and dopamine cells within the nigrostriatal pathway undergo profound degeneration. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the production of all catecholamines, including dopamine and noradrenaline, and is selectively expressed in the cells that produce these neurotransmitters. In vitro studies have previously shown that the TH-synthetic system can contribute to the formation of reactive oxygen species. In addition, animal models of dopamine mishandling demonstrated that free dopamine is neurotoxic. To examine how increased TH activity might influence catecholamine systems in vivo, we generated TH-overexpressing mice (TH-HI) with six total copies of the TH murine gene. A commensurate increase in TH mRNA produced a threefold increase in both total TH protein and phosphorylated TH levels. We found an increased rate of dopamine synthesis in both young and adult mice, reflected by the accumulation of L-DOPA following NSD-1015 administration, as well as elevated dopamine tissue content in young mice and an increased presence of dopamine metabolites at both ages. Adult mice show no difference in baseline locomotor behaviour compared to wildtype littermates, but a have potentiated response to amphetamine. In addition to elevated dopamine turnover in the striatum, TH-HI mice show reduced levels of glutathione and increased levels of cysteinylated catechols. These results indicate that a heightened level of active TH can produce oxidative stress, and may represent a source of toxicity that is specific to catecholamine cells, which are most vulnerable to degeneration in Parkinsons disease.

neuroscience↗