[18F]GE-180-PET and Post Mortem Marker Characteristics of Long-Term High-Fat-Diet-Induced Chronic Neuroinflammation in Mice.

Obesity is characterized by immoderate fat accumulation leading to an elevated risk of neurodegenerative disorders, along with a host of metabolic disturbances. Chronic neuroinflammation is a main factor linking obesity and the propensity for neurodegenerative disorders. To determine the cerebrometabolic effects of diet-induced obesity (DIO) in female mice fed a long-term (24 weeks) high-fat diet (HFD, 60% fat) compared to a group on a control diet (CD, 20% fat), we used in vivo PET imaging with the radiotracer [18F]FDG as a marker for brain glucose metabolism. In addition, we determined the effects of DIO on cerebral neuroinflammation using translocator protein 18 kDa (TSPO)-sensitive PET imaging with [18F]GE-180. Finally, we performed complementary post mortem histological and biochemical analyses of TSPO and further microglial (Iba1, TMEM119) and astroglial (GFAP) markers as well as cerebral expression analyses of cytokines (e.g., Interleukin (IL)-1ß). We showed the development of a peripheral DIO phenotype, characterized by increased body weight, visceral fat, free triglycerides and leptin in plasma, as well as increased fasted blood glucose levels. Furthermore, we found obesity-associated hypermetabolic changes in brain glucose metabolism in the HFD group. Our main findings with respect to neuroinflammation were that neither [18F]GE-180 PET nor histological analyses of brain samples seem fit to detect the predicted cerebral inflammation response, despite clear evidence of perturbed brain metabolism along with elevated IL-1ß expression. These results could be interpreted as a metabolically activated state in brain-resident immune cells due to a long-term HFD.

Leptin deficiency-caused behavioral change - A comparative analysis using EthoVision and DeepLabCut.

Introduction: Obese rodents e.g., the leptin-deficient (ob/ob) mouse exhibit remarkable behavioral changes and are therefore ideal models for evaluating mental disorders resulting from obesity. In doing so, female as well as male ob/ob mice at 8, 24, and 40 weeks of age underwent two common behavioral tests, namely the Open Field test and Elevated Plus Maze, to investigate behavioral alteration in a sex- and age dependent manner. The accuracy of these tests is often dependent on the observer that can subjectively influence the data. Methods: To avoid this bias, mice were tracked with a video system. Video files were further analyzed by the compared use of two software, namely EthoVision (EV) and DeepLabCut (DLC). In DLC a Deep Learning application forms the basis for using artificial intelligence in behavioral research in the future, also with regard to the reduction of animal numbers. Results: After no sex and partly also no age-related differences were found, comparison revealed that both software lead to almost identical results and are therefore similar in their basic outcomes, especially in the determination of velocity and total distance movement. Moreover, we observed additional benefits of DLC compared to EV as it enabled the interpretation of more complex behavior, such as rearing and leaning, in an automated manner. Discussion: Based on the comparable results from both software, our study can serve as a starting point for investigating behavioral alterations in preclinical studies of obesity by using DLC to optimize and probably to predict behavioral observations in the future.

Fibroblast Growth Factor 21 as a Potential Biomarker for Improved Locomotion and Olfaction Detection Ability after Weight Reduction in Obese Mice.

Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The aim of this study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with decreased plasma FGF21 levels. After establishing a model for diet-induced obesity, mice were subjected to three different interventions for weight reduction, namely dietary change, treadmill exercise, or time-restricted feeding. In this study, we demonstrated that only the combination of dietary change and treadmill exercise affected all parameters leading to a reduction in weight, fat, and FGF21, as well as less anxious behaviour, higher overall activity, and improved olfactory detection abilities. To investigate the interrelationship between FGF21 and behavioural parameters, feature selection algorithms were applied designating FGF21 and body weight as one of five highly weighted features. In conclusion, we concluded from the complementary methods that FGF21 can be considered as a potential biomarker for improved behaviour in obese mice after weight reduction.

PREDATORY INTERACTION BETWEEN TWO ANURAN SPECIES WITH Thamnodynastes chaquensis (COLUBRIDAE) IN THE BRAZILIAN CERRADO / Interacción depredatoria entre dos especies de anura con Thamnodynastes chaquensis (Colubridae) en el Cerrado brasileño

ABSTRACT Although predatory events are uncommon to be recorded in nature, these data are important tools for understanding prey-predator interaction of the involved species. Snakes of genus Thamnodynastes are known for having an anuran diet, including some species of hylid frogs in their diet. Despite this, this pattern does not include T. chaquensis since there are no records on predation or trophic interaction with hylid frogs. Here, we report the first predatory interaction between T. chaquensis and two hylid frogs in Brazilian Cerrado. The first predation event with treefrog Boana caiapo occurred with success but, the second with B. albopunctata did not. Connecting trophic links within an ecosystem requires in-depth knowledge of its species and their intraspecific interactions. In this context, records of the predation and predation attempts such as these may help to connect unknown trophic links, which helps to understand aspects of the natural history of the species involved.

RESUMEN Aunque los eventos depredatorios son poco comunes de registrar en la naturaleza, estos datos son herramientas importantes para comprender la interacción presa-depredador de las especies involucradas. Las serpientes del género Thamnodynastes son conocidas por su dieta basada en anuros y, aunque algunas especies incluyen ranas hílidas en su dieta, esto no ocurre en la especie T. chaquensis porque no hay registros de depredación o interacción trófica con los hílidos. Aquí informamos sobre la primera interacción depredatoria entre T. chaquensis y dos ranas hílidas del Cerrado brasileño. El primer evento de depredación con la rana Boana caiapo fue exitoso, pero el segundo con B. albopunctata no. Conectar los enlaces tróficos dentro de un ecosistema requiere conocer íntimamente sus especies y sus interacciones intraespecíficas. En este contexto, los registros de depredación y de intentos de depredación como estos pueden ayudar a conectar enlaces tróficos no conocidos, lo cual ayuda a comprender los aspectos de la historia natural de las especies involucradas.