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La Porta, C.

Publications and source records attributed to La Porta, C..

2 recordsLinked to original sources

Experimenter familiarization is a crucial prerequisite for assessing behavioral outcomes and reduces stress in mice not only under chronic pain conditions

ABSTARCTRodent behavior is affected by different environmental conditions. These do not only comprise experimental and housing conditions but also familiarization with the experimenter. However, specific effects on pain-related behavior and chronic pain conditions have not been examined. Therefore, we aimed to investigate the impact of different housing conditions, inverted day-night cycles, and experimenter familiarization on male mice following peripheral neuropathy using the spared nerve injury (SNI) model. Using a multimodal approach, we evaluated evoked pain-related-, anxiety- and depression-like behavior, corticosterone metabolite levels and utilized an integrative approach for relative-severity-assessment. Different environmental conditions are represented by individually ventilated cages and standard open cages combined with a reversed day-night-light cycle and experimenter habituation, inducing differentially modulated multidimensional pain- and emotion-like phenotypes in SNI mice. In addition, familiarization reduced the stress level caused by behavioral tests. Although no environmental condition significantly modulated the severity in SNI mice, it influenced pain-affected phenotypes and is, therefore, crucial for designing and interpreting preclinical pain studies. Moreover, environmental conditions should be considered more in the reporting guidelines, described in more detail, and discussed as a potential influence on pain phenotypes.

animal behavior and cognition↗

Identifying inhibitors of epithelial-mesenchymal plasticity using a network topology based approach

Metastasis is the cause of over 90% of cancer-related deaths. Cancer cells undergoing metastasis can switch dynamically between different phenotypes, enabling them to adapt to harsh challenges such as overcoming anoikis and evading immune response. This ability, known as phenotypic plasticity, is crucial for the survival of cancer cells during metastasis, as well as acquiring therapy resistance. Various biochemical networks have been identified to contribute to phenotypic plasticity, but how plasticity emerges from the dynamics of these networks remains elusive. Here, we investigated the dynamics of various regulatory networks implicated in Epithelial-Mesenchymal Plasticity (EMP) - an important arm of phenotypic plasticity - through two different mathematical modelling frameworks: a discrete, parameter-independent framework (Boolean) and a continuous, parameter-agnostic modelling framework (RACIPE). Results from either framework in terms of phenotypic distributions obtained from a given EMP network are qualitatively similar and suggest that these networks are multi-stable and can give rise to phenotypic plasticity. Neither method requires specific kinetic parameters, thus our results emphasize that EMP can emerge through these networks over a wide range of parameter sets, elucidating the importance of network topology in enabling phenotypic plasticity. Furthermore, we show that the ability to exhibit phenotypic plasticity correlates positively with the number of positive feedback loops in a given network. These results pave a way towards an unorthodox network topology-based approach to identify crucial links in a given EMP network that can reduce phenotypic plasticity and possibly inhibit metastasis - by reducing the number of positive feedback loops.

systems biology↗