Biology subjects

Weihrauch, D.

Publications and source records attributed to Weihrauch, D..

3 recordsLinked to original sources

bioRxiv2025

Rat Hindlimb Amputation Model Shows Analgesia and Sexually Dimorphic Cold Hypersensitivity with Immediate Targeted Muscle Reinnervation

IntroductionTargeted muscle reinnervation (TMR) has been used clinically to reduce pain in amputees but the mechanisms producing analgesia are unknown. Here we employ rat hindlimb amputation as an appropriate model to evaluate algogenic processes affected by TMR, performed at the time of amputation in subjects of both sex. MethodsAdult male and female Sprague-Dawley rats were assigned to amputation-only or amputation + immediate TMR (iTMR). Reflexive pain behaviors (von Frey, pin, and cold hypersensitivity testing) and spontaneous pain behaviors (guarding, flinching, anhedonia from loss of sucrose preference) were assessed. Retrograde labeling distinguished sensory and motor neurons and identified nerve coaptation sites. ResultsiTMR reduced hyperalgesia and anhedonia that followed amputation. By 4 weeks, pin testing showed reduced pain responses in iTMR rats (25%) versus amputation-only (51%, p=0.01). Sucrose preference testing revealed reduced anhedonia in iTMR rats (76% vs. 43%, p=0.01). Response to cold diminished in male iTMR rats (49% vs. 100% in amputation-only males, p<0.001), but not in females. Histology showed neuroma formation in controls but not after iTMR. Both sensory and motor fibers entered the motor branch after iTMR. ConclusionsThese findings show iTMR prevents neuroma formation and provides analgesia after amputation and, while its effect on cold hypersensitivity is sexually dimorphic. This supports further investigation into TMR analgesic mechanisms, the utility of the hindlimb amputation model, and the need for sex-specific evaluations. PerspectiveUsing a rat hindlimb amputation model to evaluate iTMR, we demonstrate its potential to mitigate neuropathic pain and neuroma formation and reveal sex-specific responses to cold hypersensitivity. These findings indicate the potential clinical utility of iTMR in improving pain outcomes, potentially providing more tailored approaches to pain management in amputees.

animal behavior and cognition↗

bioRxiv2023

Integrated organismal responses induced by ecologically-relevant pCO2 and temperature exposures in developing lake sturgeon

Atmospheric CO2 and temperature are rising concurrently, and may have profound impacts on the transcriptional, physiological, and behavioral responses of aquatic organisms. Further, spring snow melt may cause transient increases of pCO2 in freshwater systems. Lake sturgeon (Acipenser fulvescens) groups were raised in current and projected levels of warming and pCO2. Following an overwintering period, lake sturgeon were exposed to a transient increase in pCO2, simulating a spring melt. Diverging transcriptional patterns were found in each group and metabolic rate was lower in the combined stressor group compared to others. Behavioral assays revealed no effect of environment on alarm cue responses or boldness, but there was a decrease in total activity following an acute CO2 exposure. These results demonstrate compensatory and compounding mechanisms of pCO2 and warming dependent on developmental conditions of a freshwater fish, and provide key information for responses to future climate change.

zoology↗

bioRxiv2021

A novel nitrogen concentrating mechanism in the coral-algae symbiosome

Coral algal symbionts are hosted inside the symbiosome of gastrodermal cells, an intracellular compartment that isolates algae from the external environment and allows host cells to control the delivery of metabolites to their symbionts. However, the underlying molecular mechanisms are largely unknown. Here, we report the diel trafficking of NH3-transporting Rhesus (Rh) channels between the cytoplasm and the symbiosome membrane in the coral Acropora yongei, which matches established patterns of nitrogen delivery to endosymbionts. Heterologous expression in Xenopus oocytes established that A. yongei Rh (ayRhp1) is a channel that facilitates NH3 diffusion across membranes following its partial pressure gradient. Immunostaining revealed ayRhp1 is widely distributed throughout coral tissues and most abundantly present in oral ectodermal cells, desmocytes, and gastrodermal cells. In the latter, ayRhp1 was observed in the symbiosome membrane of alga-containing cells. Together with V-type H+-ATPases that make the symbiosome highly acidic (pH~4), ayRhp1 constitutes an NH4+-trapping mechanism analogous to that in mammalian renal tubule. Remarkably, ayRhp1 presence in the symbiosome membrane was higher during the day than the night. This indicates a regulatory mechanism that facilitates NH4+ delivery to alga during the day, likely to sustain high turnover rates of photosynthetic proteins, while restricting NH4+ delivery at night to maintain the endosymbiotic algae in a nitrogen-limited stage that stagnates their growth. The dynamic trafficking of proteins to and away from the symbiosome membrane is a previously unknown mechanism that contributes to metabolic regulation between symbiotic partners. Significance StatementThe endosymbiotic relationship between corals and algae relies on the coordinated exchange of metabolites. Disruption of these metabolic exchanges can result in interruption of the symbiosis; however, the underlying molecular mechanisms are poorly understood. Here we report that Acropora yongei coral host cells express ammonia-transporting channel proteins (ayRhp1), which traffic to and away from the symbiosome membrane surrounding the endosymbiotic algae. In conjunction with the acidic symbiosome microenvironment, this mechanism allows host cells to regulate nitrogen delivery to endosymbionts sustaining essential functions while restricting growth. This work provides novel mechanistic information about metabolic regulation of animal-algae symbioses, and advances our understanding of physiological mechanisms that might determine coral local adaptation, resilience, and vulnerability to environmental stress including climate change.

physiology↗