High-carbohydrate and fat diet consumption causes metabolic deterioration, neuronal damage, and loss of recognition memory in rats.

The number of people diagnosed with metabolic syndrome (MetS) has increased dramatically to reach alarming proportions worldwide. The origin of MetS derives from bad eating habits and sedentary lifestyle. Most people consume foods high in carbohydrates and saturated fat. In recent years, it has been reported that alterations in insulin at the brain level could have an impact on the appearance of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, dementia, depression, and other types of disorders that compromise brain function. These alterations have been associated with damage to the structure and function of neurons located in the reptilian and limbic systems, a decrease in dendritic arborization and an exacerbated inflammatory state that impaired learning and memory and increased in the state of stress and anxiety. Although the molecular mechanisms induced by MetS to cause neurodegeneration are not fully understood. The aim of this study is to know the effect of the intake of hypercaloric diets on the structure and function of neurons located in the frontal cortex, hypothalamus and hippocampus and its impact on behavior in rats with metabolic syndrome. In conclusion, the present study illustrated that chronic exposure to hypercaloric diets, with a high content of sugars and saturated fatty acids, induces a proinflammatory state and exacerbates oxidative stress in brain regions such as the hypothalamus, hippocampus, and frontal cortex, leading to dysfunction. metabolism, neuronal damage, and recognition memory loss.

Ketorolac and (-)-Epicatechin change retinal GFAP and NRF2 expression on hyperglycemic CD1 mice.

Our objective was to determine whether (-)-Epicatechin administered alone or simultaneously with topical Ketorolac decreased the relative expression of GFAP and modulated the response of Nrf2 in a mouse model with induced hyperglycemia. We found that GFAP and Nrf2 decreased in the groups that received treatments alone or simultaneous during 8 weeks; even when the effect on the Nrf2 was not pronounced, it showed a higher concentration when GFAP decreased. Our results suggest a protective effect of Ketorolac and (-) - Epicatechin, which seem to limit the preclinical retinal damage caused by inflammation in hyperglycemia.

Bezafibrate In Vivo Administration Prevents 3-Methylglutaric Acid-Induced Impairment of Redox Status, Mitochondrial Biogenesis, and Neural Injury in Brain of Developing Rats.

3-Methylglutaric acid (MGA) is an organic acid that accumulates in 3-methylglutaconic (MGTA) and 3-hydroxy-3-methylglutaric (HMGA) acidurias. Patients affected by these disorders present with neurological dysfunction that usually appears in the first years of life. In order to elucidate the pathomechanisms underlying the brain injury in these disorders, we evaluated the effects of MGA administration on redox homeostasis, mitochondrial respiratory chain activity, and biogenesis in the cerebral cortex of developing rats. Neural damage markers and signaling pathways involved in cell survival, and death were also measured after MGA administration. Furthermore, since the treatment for MGTA and HMGA is still limited, we tested whether a pre-treatment with the pan-peroxisome proliferator-activated receptor (PPAR) agonist bezafibrate could prevent the alterations caused by MGA. MGA provoked lipid peroxidation, increased heme oxygenase-1 content, and altered the activities of antioxidant enzymes, strongly suggestive of oxidative stress. MGA also impaired mitochondrial function and biogenesis by decreasing the activities of succinate dehydrogenase and various respiratory chain complexes, as well as the nuclear levels of PGC-1α and NT-PGC-1α, and cell content of Sirt1. AMPKα1 was further increased by MGA. Neural cell damage was also observed following the MGA administration, as verified by decreased Akt and synaptophysin content and reduced ERK phosphorylation, and by the increase of active caspase-3 and p38 and Tau phosphorylation. Importantly, bezafibrate prevented MGA-elicited toxic effects towards mitochondrial function, redox homeostasis, and neural cell injury, implying that this compound may be potentially used as an adjunct therapy for MGTA and HMGA and other disorders with mitochondrial dysfunction.