Biology subjects

Soto, P.

Publications and source records attributed to Soto, P..

5 recordsLinked to original sources

bioRxiv2024

Long-Term Effects of Early Adolescent Second-Generation Antipsychotic Exposure on Body Weight, Caloric Intake, and Metabolism-Associated Gene Expression

The use of second-generation antipsychotic (SGA) medications in pediatric patients raises concerns about potential long-term adverse outcomes. The current study evaluated the long-term effects of treatment with risperidone or olanzapine on body weight, caloric intake, serum insulin, blood glucose, and metabolism-associated gene expression in C57Bl/6J female mice. Compared to mice treated with vehicle, female mice treated with risperidone or olanzapine gained weight at higher rates during treatment and maintained higher body weights for months following treatment cessation. During high-fat diet feeding, some groups of treated mice gained weight at higher rates than their respective control groups, but the finding was not consistent across experiments. Finally, female mice previously treated with olanzapine also exhibited increased expression of genes associated with inflammation and lipogenesis. These findings suggest that pediatric use of SGA medications that induce excess weight gain during treatment may exert persistent effects on body weight and gene expression and such outcomes may form an important aspect of assessing risk-to-benefit ratios in prescribing decisions.

pharmacology and toxicology↗

bioRxiv2024

Persistent Behavioral and Physiological Effects of Dietary Protein Restriction

Protein provides essential amino acids critical for survival. Recent research has identified that dietary protein restriction induces physiological and behavioral adaptations and that those adaptations are mediated by liver-produced fibroblast growth factor 21 (FGF21) that acts in the brain. Most of the research on adaptations to dietary protein restriction and the biological factors that mediate those adaptations carries an implicit assumption that the effects of dietary protein restriction are reversible. Rarely is the assumption of reversibility directly examined by varying dietary protein content within animals. Recently collected data on preference for protein versus carbohydrate solutions indicates that when mice are placed on a low (5%) protein diet, preference for protein is rapidly increased. However, when mice are switched from a low to normal (20%) protein diet, relative consumption of protein decreases but preference for protein persists. Re-analysis of published data suggests, similarly, that preference for protein-rich food sources remains elevated following exposure to dietary protein restriction and that calcium influx in the ventral tegmental area of the brain in response to protein consumption also remains persistently elevated following dietary protein restriction. Together, the data suggest that prior protein restriction can exert long-lasting effects on protein preference and on brain activity associated with protein consumption. The finding that the effects of protein restriction do not rapidly reverse implies that protein choice may be a function, not only of current nutritional state, but of historical nutritional conditions. Further, these results suggest that a full understanding of the environmental and biological determinants of protein choice requires studies in which dietary protein intake is varied within subjects.

animal behavior and cognition↗

bioRxiv2024

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation as compared to casein in control-fed mice, whereas casein triggered a larger activation in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice. These data strongly suggest that the increased FGF21 during protein restriction acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

neuroscience↗

bioRxiv2021

Gene function prediction in five model eukaryotes based on gene relative location through machine learning

MotiviationThe function of most genes is unknown. The best results in gene function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a genes function is not independent of its location, the few available examples of gene function prediction based on gene location relay on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function. ResultsHere we predict thousands of gene functions in five eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models trained with features derived from the location of genes in the genomes to which they belong. To the best of our knowledge this is the first work in which gene function prediction is successfully achieved in eukaryotic genomes using predictive features derived exclusively from the relative location of the genes. Contactfpazos@iibce.edu.uy Supplementary informationhttp://gfpml.bnd.edu.uy

bioinformatics↗

bioRxiv2019

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

Parkinsons disease (PD) is the second most common neurodegenerative condition, characterized by motor impairment due to the progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine release in the striatum. Accumulating evidence suggest that degeneration of axons is an early event in the disease, involving destruction programs that are independent of the survival of the cell soma. Necroptosis, a programmed cell death process, is emerging as a mediator of neuronal loss in models of neurodegenerative diseases. Here, we demonstrate activation of necroptosis in postmortem brain tissue from PD patients and in a toxin-based mouse model of the disease. Inhibition of key components of the necroptotic pathway resulted in a significant delay of 6-hydroxydopamine dependent axonal degeneration of dopaminergic and cortical neurons in vitro. Genetic ablation of necroptosis mediators MLKL and RIPK3, as well as pharmacological inhibition of RIPK1 in vivo, decreased dopaminergic neuron degeneration, improving motor performance. Together, these findings suggest that axonal degeneration in PD is mediated by the necroptosis machinery, a process here referred to as necroaxoptosis, a druggable pathway to target dopaminergic neuronal loss.

neuroscience↗