Biology subjects

Rülicke, T.

Publications and source records attributed to Rülicke, T..

3 recordsLinked to original sources

bioRxiv2022

Large neutral amino acid levels tune perinatal neuronal excitability and survival

Surprisingly little is known about the critical metabolic changes that neural cells have to undergo during development and how even mild, temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically-relevant large neutral amino acids, lead to a form of autism spectrum disorder, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different stages of life. We found that the cerebral cortex undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes. But what are the consequences of interfering with this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of large neutral amino acids and lipids in the cerebral cortex are highly interconnected. Deletion of Slc7a5 in neurons perturbs specifically the postnatal metabolic state leading to a shift in lipid metabolism and a stage- and cell-type-specific alteration in neuronal activity patterns, resulting in a long-term cortical circuit dysfunction.

neuroscience↗

bioRxiv2022

The miR-15a/16-1 and miR-15b/16-2 clusters regulate early B cell development by limiting IL-7 receptor expression

Pleiotropic functions of miRNAs as transcriptional repressors have been reported for multiple biological processes. One prominent miRNA family is the miR-15 family, which is a well-established tumor-suppressor in B-cell chronic lymphocytic leukemia (CLL). The miR-15 family consists of three bicistronic clusters, miR-15a/16-1, miR-15b/16-2 and miR-497/195, all sharing the same seed sequence suggesting that loss one cluster can be functionally compensated by the remaining miR-15 family members. Thus, a combined deletion may be necessary to reveal its physiological function in vivo. A combined knockout of the most prominent miR-15 clusters, miR-15a/16-1 and miR-15b/16-2 in the hematopoietic system reveals a novel role of the miR-15 family in early B cell development highlighted by an increase of the pro-B cell compartment. Mechanistically, this effect is mediated by enhanced IL-7 receptor expression, which we identified as direct miR-15 target gene. Notably, elevated IL-7 receptor levels were sufficient to trigger increased activation of the STAT5 and PI3K/AKT pathways. Moreover, derepression of directly targeted cell cycle regulators such as Ccne1, Chek1 and Wee1 further facilitates G-to-S transition. Thus, by deregulating a target gene network of cell cycle and signaling mediators, loss of the miR-15 family establishes a pro-proliferative milieu manifesting in an enlarged pro-B cell pool.

immunology↗

bioRxiv2021

Effect of different ambient temperatures on reproductive outcome and wellbeing of lactating females in two mouse strains

Ambient temperature is an important non-biotic environmental factor influencing immunological and oncological parameters in laboratory mice. It is under discussion which temperature is more appropriate and whether the commonly used room temperature in rodent facilities of about 21{degrees}C represents a chronic cold stress or the 30{degrees}C of the thermoneutral zone constitutes heat stress for the animals. In this study we selected the physiological challenging period of lactation to investigate the influence of a cage temperature of 20{degrees}C, 25{degrees}C, and 30{degrees}C, respectively, on reproductive performance and stress hormone levels in two frequently used mouse strains. We found that more pups were weaned from B6D2F1 hybrids compared to C57BL/6N mothers and that the number of weaned pups was strongly reduced if mothers of both strains were kept at 30{degrees}C. Furthermore, at 30{degrees}C mothers and pups showed reduced body weight at weaning and offspring had longer tails. Despite pronounced temperature effects on reproductive parameters, we did not find any impact on adrenocortical activity in breeding and control mice. Independent of the ambient temperature however, we found that females raising pups showed elevated levels of fecal corticosterone metabolites (FCMs) compared to controls. Increased levels of stress hormone metabolites were measured specially around birth and during the third week of lactation. Our results provide no evidence for reduced or improved wellbeing of lactating mice at different ambient temperatures, but we found that a 30{degrees}C cage temperature impairs reproductive performance.

physiology↗