Biology subjects

Jensen, A. L.

Publications and source records attributed to Jensen, A. L..

4 recordsLinked to original sources

bioRxiv2025

Influence of solvent, sex, and age on pharmacokinetic and acute behavioral effects of vaporized cannabis extract in mice

The legalization of cannabis in several states across the US has increased the need to better understand its effects on the body, brain, and behavior, particularly in different populations. Rodent models are particularly valuable in this respect because they provide precise control over external variables. Previous rodent studies have found age and sex differences in response to injected {Delta}9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis. However, this route of administration does not mimic the most common way humans consume cannabis, i.e. through inhalation. Here, we sought to address this gap by investigating age and sex differences in pharmacokinetics and the acute behavioral effects of vaporized cannabis extract in mice. Adolescent (postnatal day [P] 35-50) and adult ([≥] P70) mice of both sexes received noncontingent exposure to 0 mg/ml, 150 mg/ml, or 300 mg/ml vaporized cannabis extract diluted in either 80% propylene glycol/20% vegetable glycerol (PG/VG) or 100% polyethylene glycol 400 (PEG). Immediately after exposure, body temperature, hot plate withdrawal latency, and locomotion were assessed. Blood was collected at 0, 30, and 60 min after vapor exposure, and plasma THC and its metabolites were analyzed. Measured THC levels were higher in both the plasma of vapor-exposed mice and the cannabis extract solutions themselves when PEG was the solvent compared to PG/VG. Vaporized cannabis (dissolved in PEG) at the highest dose tested induced hypothermic, antinociceptive, and locomotor-suppressing effects in all groups of mice. We found a dose-dependent age difference in locomotion, indicating that adolescents were less sensitive to the locomotor-suppressing effects of vaporized cannabis, which may be related to the plasma THC levels achieved. Although we found no significant sex differences in the acute behavioral effects of vaporized cannabis, there were significant sex differences in plasma THC metabolites indicating that female mice may metabolize vaporized cannabis more slowly than male mice. Taken together, the current findings add to a growing number of studies implementing vaporized cannabinoid delivery approaches by revealing PEG as the superior solvent for studies involving cannabis extract.

animal behavior and cognition↗

bioRxiv2024

Mapping atherogenesis mechanisms in smooth muscle cells by targeting genes linked to coronary artery disease

Recent genome-wide association studies (GWAS) have identified multiple vascular cell-expressed genes linked to coronary artery disease (CAD), suggesting that smooth muscle cells (SMCs) and SMC-derived metaplastic cells are promising targets for novel antiatherosclerosis therapies. However, the disease-promoting pathways of most GWAS-identified genes are unknown, hindering their translation into therapeutic targets. This study integrated public GWAS data for CAD and single-cell RNA sequencing (scRNA-seq) analyses of human atherosclerotic plaques to identify 20 GWAS risk genes with a putative mechanism of action in SMCs or SMC-derived cells. Gene perturbation experiments in SMCs coaxed to plaque-relevant phenotypes revealed that the selected risk genes, despite encoding very different types of proteins, regulated shared sets of genes associated with contractile functions, cell cycle pathways, NF{kappa}B, and type I interferon signaling. By integrating information about GWAS gene effect direction and a deep analysis of cholesterol- and stretch-induced gene modules in SMCs, we find evidence that cholesterol-induced signaling is a pro-atherogenic disease mechanism in SMCs that is upregulated by detrimental and downregulated by protective GWAS genes. Overall, our study identifies a set of candidate disease mechanisms in SMCs that are regulated by multiple GWAS genes across several SMC assays. Furthermore, it provides proof-of-concept for using GWAS gene effect directionality to predict the pathogenic effect of candidate disease mechanisms that can be extended to other GWAS genes and cell types in the future.

cell biology↗

bioRxiv2022

Sex and timing of gonadectomy relative to puberty interact to influence weight, body composition, and feeding behaviors in mice

Gonadal sex steroids are important regulators of energy balance in adult rodents, and gonadectomy (GDX) has opposing effects on weight gain in sexually mature males and females. Puberty is associated with the emergence of sex differences in weight, body composition, and feeding behaviors, yet the role of gonadal hormones at puberty remains unclear. To address this, we performed GDX or sham surgery in male and female C57Bl/6 mice at postnatal day (P)25 (prepubertal) or P60 (postpubertal) timepoints and measured weight and body composition for 35 days, after which ad libitum and operant food intake was measured using Feeding Experimentation Device 3 (FED3s) in the home cage. Consistent with previous studies, postpubertal GDX caused weight gain in females and weight loss in males and increased adiposity in both sexes. However, prepubertal GDX decreased weight gain and altered body composition across the adolescent transition (P25 to P60) in males but had no effect in females. Despite the varied effects on weight, GDX decreased food intake and motivation for food as assessed in operant tasks regardless of sex or timing of surgery relative to puberty. Our findings indicate that GDX interacts with both sex and age at surgery to influence weight, body composition, and feeding behavior. HighlightsO_LIGonadectomy had opposing effects on weight in males and females when performed in adulthood. C_LIO_LIGonadectomy performed prior to puberty decreased weight gain in males but did not affect weight gain in females. C_LIO_LIAcross sex and age at surgery, GDX decreased ad libitum food intake and reduced operant responding for food. C_LIO_LIDecreased food intake under effortful conditions was not explained by body weight in GDX mice. C_LI

animal behavior and cognition↗

bioRxiv2021

Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via Proteomics of Isolated Chromatin fragments, applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.

microbiology↗