ABSTRACT
Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.
Subject(s)
Diet, Ketogenic , Oxidative Stress , Animals , Male , Mice , Oxidative Stress/physiology , Memory Disorders/metabolism , Memory Disorders/etiology , Neuroinflammatory Diseases/metabolism , Diet, Carbohydrate-Restricted , Fasting/metabolism , Energy Metabolism/physiology , Brain/metabolismABSTRACT
Animal models of cerebral ischemia have improved our understanding of the pathophysiology and mechanisms involved in stroke, as well as the investigation of potential therapies. The potential of zebrafish to model human diseases has become increasingly evident. The availability of these models allows for an increased understanding of the role of chemical exposure in human conditions and provides essential tools for mechanistic studies of disease. To evaluate the potential neuroprotective properties of minocycline against ischemia and reperfusion injury in zebrafish and compare them with other standardized models. In vitro studies with BV-2 cells were performed, and mammalian transient middle cerebral artery occlusion (tMCAO) was used as a comparative standard with the zebrafish stroke model. Animals were subjected to ischemia and reperfusion injury protocols and treated with minocycline. Infarction size, cytokine levels, oxidative stress, glutamate toxicity, and immunofluorescence for microglial activation, and behavioral test results were determined and compared. Administration of minocycline provided significant protection in the three stroke models in different parameters analyzed. Both experimental models complement each other in their particularities. The proposal also strengthens the findings in the literature in rodent models and allows the validation of alternative models so that they can be used in further research involving diseases with ischemia and reperfusion injury.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Reperfusion Injury , Stroke , Animals , Humans , Zebrafish , Minocycline/pharmacology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Stroke/drug therapy , Brain Ischemia/drug therapy , Infarction, Middle Cerebral Artery/drug therapy , Reperfusion Injury/drug therapy , Disease Models, Animal , MammalsABSTRACT
The study evaluated the effects of supplementation with three different probiotic strains Bifidobacterium lactis (LACT GB™), Lactobacillus rhamnosus (RHAM GB™) and Lactobacillus reuteri (REUT GB™) on brain-intestinal immunomodulation in an animal model of LPS-induced inflammation. Fifty mice Balb/C were distributed into five groups: control; lipopolysaccharide (LPS); LPS + B. lactis (LACT GB™); LPS + L. rhamnosus (RHAM GB™); and LPS + L. reuteri (REUT GB™). The animals were supplemented with their respective probiotic microorganisms daily, for 30 days, at a concentration of 1 × 109 CFU/animal/day. After 30 days of supplementation, animals received the inflammatory insult by LPS (15 mg/kg). Behavioral tests, oxidative stress and inflammation were performed, as well as gut and brain histology. In the behavioral test, LPS + B. lactis group was less anxious than the other groups. Serum interleukin IL-1ß and IL-6 levels increased in all groups that received the LPS insult, and there was a reduction in inflammation in the supplemented groups when compared to the LPS group in brain and gut. There is a reduction in myeloperoxidase activity and oxidative stress in groups supplemented with probiotics. In intestine histological analysis occurs damage to the tissue integrity in the LPS group, in the other hand, occurs preservation of integrity in the probiotic supplemented animals. In the brain, infiltrates of perivascular inflammatory cells can be seen in the LPS group. The three probiotic studies showed efficient immunomodulating activity and ensured integrity of the intestinal barrier function, even after the severe insult by LPS. These results show the important role of probiotics in the gut-brain axis. Graphical abstract illustratively represents the gut-brain axis and how different probiotic strains influence the immunomodulatory response releasing different pro- and anti-inflammatory cytokines, and their role in the balance of dysbiosis.
