Biology subjects

Rullman, E.

Publications and source records attributed to Rullman, E..

5 recordsLinked to original sources

bioRxiv2023

Bouts of rest and physical activity in C57BL/6J mice

The objective was to exploit the raw data output from a scalable home cage (type IIL IVC) monitoring (HCM) system (DVC(R)), to characterize pattern of undisrupted rest and physical activity (PA) of C57BL/6J mice. The systems tracking algorithm show that mice in isolation spend 67% of the time in bouts of long rest ([≥]40s) and 59 % of the time was interpreted as sleep. Twenty percent is physical activity (PA), split equally between local movements and locomotion. Decomposition revealed that a day contains [~]6500 discrete bouts of short and long rest, local and locomotor movements. Mice travel [~]330m per day, mainly during the dark hours, while travelling speed is similar through the light-dark cycle. Locomotor bouts are usually <0.2m and <1% are >1m. Tracking revealed also fits of abnormal behaviour. The starting positions of the bouts showed no preference for the rear over the front of the cage floor, while there was a strong bias for the peripheral (75%) over the central floor area. The composition of bouts has a characteristic circadian pattern, however, intrusive husbandry routines increased bout fragmentation by [~]40%. Extracting electrode activations density (EAD) from the raw data yielded results close to those obtained with the tracking algorithm, with 59% of time in long rest (<1 EAD s-1) and 20% in PA. We confirm that EAD correlates closely with movement distance (rs >0.95) and the data agreed in [~]96% of the file time. Thus, albeit EAD being less informative it may serve as a proxy for PA and rest, enabling monitoring group housed mice. The data show that a change in housing density from one to two, and up to three mice had the same effect size on EAD ([~]2) with no difference between sexes. The EAD deviated significantly from this stepwise increase with 4 mice per cage, suggesting a crowdedness stress inducing sex specific adaptations. We conclude that informative metrics on rest and PA can be automatically extracted from the raw data flow in near-real time (< 1 hrs). These metrics relay useful longitudinal information to those that use or care for the animals.

animal behavior and cognition↗

bioRxiv2022

PCYT2 controls muscle health and muscle aging

Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing, affecting hundreds of millions of people. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases represents an important goal in improving human health. Here, we show that phosphatidylethanolamine cytidyltransferase (PCYT2/ECT), the critical enzyme of the Kennedy branch of phosphatidylethanolamine (PE) synthesis pathway, has an essential role in muscle health. Human genetic deficiency in PCYT2 causes a severe disease with failure to thrive and progressive muscle weakness. Pcyt2 mutant zebrafish recapitulate the patient phenotypes, indicating that the role of PCYT2/PE in muscle is evolutionary conserved. Muscle specific Pcyt2 knockout mice exhibited failure to thrive, impaired muscle development, progressive muscle weakness, muscle loss, accelerated ageing, and reduced lifespan. Mechanistically, Pcyt2 deficiency affects mitochondrial bioenergetics and physicochemical properties of the myofiber membrane lipid bilayer, in particular under exercise strain. We also show that PCYT2 activity declines in the aging muscles of humans and mice. AAV-based delivery of PCYT2 rescued muscle weakness in Pcyt2 knock-out mice and, importantly, improved muscle strength in old mice, offering a novel therapeutic avenue for rare disease patients and muscle aging. Thus, PCYT2 plays a fundamental, specific, and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2 synthesized PE lipids to severe muscle dystrophy, exercise intolerance and aging.

genetics↗

bioRxiv2021

Glucose intolerance in aging is mediated by the Gpcpd1-GPC metabolic axis

Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, muscle mediated metabolic homeostasis is perturbed, contributing to the onset of multiple chronic diseases. Our knowledge on the mechanisms responsible for this age-related perturbation is limited, as it is difficult to distinguish between correlation and causality of molecular changes in muscle aging. Glycerophosphocholine phosphodiesterase 1 (GPCPD1) is a highly abundant muscle enzyme responsible for the hydrolysis of the lipid glycerophosphocholine (GPC). The physiological function of GPCPD1 remained largely unknown. Here, we report that the GPCPD1-GPC metabolic pathway is dramatically perturbed in the aged muscle. Muscle-specific inactivation of Gpcpd1 resulted in severely affected glucose metabolism, without affecting muscle development. This pathology was muscle specific and did not occur in white fat-, brown fat- and liver-deficient Gpcpd1 deficient mice. Moreover, in the muscle specific mutant mice, glucose intolerance was markedly accelerated under high sugar and high fat diet. Mechanistically, Gpcpd1 deficiency results in accumulation of GPC, without any other significant changes in the global lipidome. This causes an "aged-like" transcriptomic signature in young Gpcpd1 deficient muscles and impaired insulin signaling. Finally, we report that GPC levels are markedly perturbed in muscles from both aged humans and patients with Type 2 diabetes, with a high correlation between GPC levels and increased chronological age. Our findings show the novel and critical physiological function of GPCPD1-GPC metabolic pathway to glucose metabolism, and the perturbation of this pathway with aging, which may contribute to glucose intolerance in aging.

physiology↗

bioRxiv2020

Major oscillations in spontaneous home-cage activity with an infraradian periodicity in C57Bl/6 mice housed under constant conditions

Using 14-20 months of cumulative 24/7 home-cage activity recorded with a non-intrusive technique and a data driven analytical approach, we here provide evidence for the existence of a circannual oscillation (1-2 SD of the mean, on average 65% higher during peak of highs than lows; P=7E-50) in spontaneous activity of male and female C57BL/6 mice held under constant barrier conditions (dark-light cycle 12/12 h (DL), temperature 21{+/-}1{degrees}C, humidity 40-60%). The periodicity of the season-like oscillation is in the range of 2-4 months (on average 97 days across cohorts of cages) and off-sets also responses to environmental stimuli but does not significantly alter the preference for activity during the dark hours of this nocturnal mouse strain (P=0.11 difference between highs and lows). The significance of this hitherto not recognized slow rhythmic alteration in spontaneous activity is further substantiated by its co-variation with the feeding behaviour of the mice. The absence of coordination within and between cohorts of cages or synchronization to the seasons of the year, suggests that the oscillation of in-cage activity and behavioural responses is generated by a free-running intrinsic oscillator devoid of synchronization with an out-of-cage environmental time-keeper. Since the variation over time has such a magnitude and correlate with the feeding behaviour it is likely that it will impact a range of long term experiments conducted on laboratory mice if left unrecognized.

animal behavior and cognition↗

bioRxiv2019

Muscle strength, size and composition following 12 months of gender-affirming treatment in transgender individuals: retained advantage for the transwomen

ObjectivesThis study explored the effects of gender-affirming treatment, which includes inhibition of endogenous sex hormones and replacement with cross-sex hormones, on muscle function, size and composition in 11 transwomen (TW) and 12 transmen (TM).\n\nMethodsIsokinetic knee extensor and flexor muscle strength was assessed at baseline (T00), 4 weeks after gonadal suppression of endogenous hormones but before hormone replacement (T0), and 3 (T3) and 11 (T12) months after hormone replacement. In addition, at T00 and T12, we assessed lower-limb muscle volume using MRI, and cross-sectional area (CSA) and radiological density using CT.\n\nResultsThigh muscle volume increased (15%) in TM, which was paralleled by increased quadriceps CSA (15%) and radiological density (6%). In TW, the corresponding parameters decreased by -5% (muscle volume) and -4% (CSA), while density remained unaltered. The TM increased strength over the assessment period, while the TW generally maintained or slightly increased in strength. Baseline muscle volume correlated highly with strength (R>0.75), yet the relative change in muscle volume and strength correlated only moderately (R=0.65 in TW and R=0.32 in TM). The absolute levels of muscle volume and knee extension strength after the intervention still favored the TW.\n\nConclusionCross-sex hormone treatment markedly affects muscle strength, size and composition in transgender individuals. Despite the robust increases in muscle mass and strength in TM, the TW were still stronger and had more muscle mass following 12 months of treatment. These findings add new knowledge that could be relevant when evaluating transwomens eligibility to compete in the womens category of athletic competitions.

physiology↗