Biology subjects

Ahrens, M.

Publications and source records attributed to Ahrens, M..

5 recordsLinked to original sources

bioRxiv2026

Macronutrient-preference is modulated by biological sex and estrous cycle in mice

Dietary choice plays a critical role in metabolic and neurological health, yet the biological factors that shape macronutrient preference remain poorly understood. Evidence from both humans and rodents suggests potential sex differences in the attractiveness of specific nutrients, though findings have been inconsistent and often rely on self-report or diets with mixed macronutrient composition. The present study examined sex differences in macronutrient preference and food-directed behavior in mice using a controlled three-food choice paradigm. Adult male (n = 12) and female (n = 11) C57BL/6J mice were given simultaneous access to foods consisting of fat, sucrose, or a fat-carbohydrate combination across 14 days. Intake, latency to approach, and time spent near each food source were quantified, and estrous cycle stage was monitored in females. Female mice consumed significantly more food than males overall, driven by a selective increase in fat intake. Behavioral measures paralleled these results, with females spending more time in proximity to fat-associated food zones. In contrast, males preferentially consumed the fat-carbohydrate combination and showed weaker nutrient-specific engagement. Estrous cycle stage modestly influenced feeding behavior, with estrus associated with increased overall intake and greater consumption of combination diets, reflecting elevated carbohydrate intake. These findings demonstrate robust sex differences in macronutrient preference and suggest that hormonal state may selectively modulate nutrient-specific feeding behavior.

neuroscience↗

bioRxiv2025

Relationship between melanoma vemurafenib tolerance thresholds and metabolic pathway choice and Wnt signaling involvement

Vemurafenib constitutes an important therapeutic for BRAFV600 mutant melanomas, but despite high initial response rates, resistance to BRAF and MEK inhibitors quickly develops. Here, we performed an integrative analysis of metabolomic consequences and transcriptome alterations to uncover mechanisms involved in adaptive vemurafenib resistance (VemR) development and their relationship with vemurafenib tolerance thresholds. We developed BRAFV600E isogenic models of VemR utilizing M14 and A2058 lines, and patient-derived melanomas with V600E or normal BRAF to verify vemurafenib selectivity. MEK or PI3K inhibitors only partially inhibited VemR cell proliferation, indicating cross-resistance to these inhibitors. MITF and {beta}-catenin levels were induced and treatment with Wnt/{beta}-catenin inhibitor ICG-001 restored vemurafenib sensitivity with concomitant reductions in {beta}-catenin-regulated gene expressions, phospho-ERK1/2, and VemR-induced mitochondrial mass and respiration. Targeted metabolite, MitoPlate-S1, Mito-stress and transcriptome/metabolomic analysis showed that melanoma cells with elevated vemurafenib tolerance thresholds such as A2058 VemR cells utilize Wnt/{beta}-catenin signaling for mitochondrial metabolism while VemR cells with low tolerance such as M14 VemR cells rely on Wnt/{beta}-catenin signaling for pentose phosphate pathway. Pathways associated with cytokine-cytokine receptor, ECM receptor, and neuroactive ligand receptor interactions were similarly enriched in BRAFV600E patient-derived melanoma as M14 and A2058 cells whereas distinct pathways involving cell cycle, DNA replication, Fanconi anemia and DNA repair pathways are upregulated in wild type BRAF expressing patient derived melanoma. These data show for the first time that the metabolic pathway choices made by VemR BRAF mutant melanomas are controlled by vemurafenib tolerance and endurance thresholds and Wnt/{beta}-catenin signaling plays a central role in coordinating expression of genes controlling VemR and metabolic pathway shifts.

cancer biology↗

bioRxiv2021

Voltage imaging identifies spinal circuits that modulate locomotor adaptation in zebrafish

Motor systems must continuously adapt their output to maintain a desired trajectory. While the spinal circuits underlying rhythmic locomotion are well described, little is known about how the network modulates its output strength. A major challenge has been the difficulty of recording from spinal neurons during behavior. Here, we use voltage imaging to map the membrane potential of glutamatergic neurons throughout the spinal cord of the larval zebrafish during fictive swimming in a virtual environment. We mapped the spiking, subthreshold dynamics, relative timing, and sub-cellular electrical propagation across large populations of simultaneously recorded cells. We validated the approach by confirming properties of known sub-types, and we characterized a yet undescribed sub-population of tonic-spiking ventral V3 neurons whose spike rate correlated with swimming strength and bout length. Optogenetic activation of V3 neurons led to stronger swimming and longer bouts but did not affect tail-beat frequency. Genetic ablation of V3 neurons led to reduced locomotor adaptation. The power of voltage imaging allowed us to identify V3 neurons as a critical driver of locomotor adaptation in zebrafish.

neuroscience↗

bioRxiv2020

A bright and high-performance genetically encoded Ca2+ indicator based on mNeonGreen fluorescent protein

Genetically encodable calcium ion (Ca2+) indicators (GECIs) based on green fluorescent proteins (GFP) are powerful tools for imaging of cell signaling and neural activity in model organisms. Following almost two decades of steady improvements in the Aequorea victoria GFP (avGFP)-based GCaMP series of GECIs, the performance of the most recent generation (i.e., GCaMP7) may have reached its practical limit due to the inherent properties of GFP. In an effort to sustain the steady progression towards ever-improved GECIs, we undertook the development of a new GECI based on the bright monomeric GFP, mNeonGreen (mNG). The resulting indicator, mNG-GECO1, is 60% brighter than GCaMP6s in vitro and provides comparable performance as demonstrated by imaging Ca2+ dynamics in cultured cells, primary neurons, and in vivo in larval zebrafish. These results suggest that mNG-GECO1 is a promising next-generation GECI that could inherit the mantle of GCaMP and allow the steady improvement of GECIs to continue for generations to come.

molecular biology↗

bioRxiv2019

A bidirectional network for appetite control in zebrafish

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

neuroscience↗