Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.

BACKGROUND: Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. METHODS: Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. RESULTS: Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1ß and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1ß, IFN-γ, RANTES, TNF-α and IL-6 levels. CONCLUSIONS: Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

Influence of anabolic steroid treatment associated to physical exercise in the ultrasonic vocalization of rats.

Unlike humans, who communicate in frequency bands between 250 Hz and 6 kHz, rats can communicate in frequencies above 18 kHz. Their vocalization types depend on the context and are normally associated to subjective or emotional states. It was reported significant vocal changes due to administration of replacement testosterone in a trained tenor singer with hypogonadism. Speech-Language Pathology clinical practices are being sought by singers who sporadically use anabolic steroids associated with physical exercise. They report difficulties in reaching and keeping high notes, "breakage" in the passage of musical notes and post singing vocal fatigue. Those abnormalities could be raised by the association of anabolic steroids and physical exercise. Thus, in order to verify if this association could promote vocal changes, maximum, minimum and fundamental frequencies and call duration in rats treated with anabolic steroids and physically trained (10 weeks duration) were evaluated. The vocalizations were obtained by handling the animals. At the end of that period, rats treated and trained showed significant decrease in call duration, but not in other parameters. The decrease in call duration could be associated to functional alterations in the vocal folds of treated and trained animals due to a synergism between anabolic steroids and physical training.

O eixo biológico do curso de Gerontologia Escola de Artes, Ciências e Humanidades – Universidade de São Paulo / The biological axis of the Gerontology Course School of Arts, Sciences and Humanities - University of São Paulo

O eixo biológico do Curso de Gerontologia da EACH-USP compreende disciplinas que exploram a construção social e histórica do conhecimento biológico, fundamenta a formação profissional com princípios da estrutura e do funcionamento dos diferentes sistemas orgânicos e introduz conceitos das principais doenças que acometem os idosos. O raciocínio científico e o crítico são estimulados, abrindo possibilidades para um processo de aprendizagem ativo, cooperativo, integrado e interdisciplinar.AU

The biological axis of the Gerontology Course of EACH-USP is composed of subjects that explore the social and historical construction of biological knowledge, provide the fundamental principles of the structure and functioning of the different organic systems and also study the main diseases that affect the elderly. Scientific and critical reasoning are stimulated, giving rise do active, cooperative, integrated and multidisciplinary learning.AU

O eixo biológico do curso de gerontologia escola de artes, ciências e humanidades: Universidade de São Paulo / The biological axis of the gerontology course school of arts, sciences and humanities: University of São Paulo

O eixo biológico do Curso de Gerontologia da EACH-USP compreende disciplinas que exploram a construção social e histórica do conhecimento biológico, fundamenta a formação profissional com princípios da estrutura e do funcionamento dos diferentes sistemas orgânicos e introduz conceitos das principais doenças que acometem os idosos. O raciocínio científico e o crítico são estimulados, abrindo possibilidades para um processo de aprendizagem ativo, cooperativo, integrado e interdisciplinar.

The biological axis of the Gerontology Course of EACH-USP is composed of subjects that explore the social and historical construction of biological knowledge, provide the fundamental principles of the structure and functioning of the different organic systems and also study the main diseases that affect the elderly. Scientific and critical reasoning are stimulated, giving rise do active, cooperative, integrated and multidisciplinary learning.

Increased expression of acetylcholine receptors in the diaphragm muscle of MDX mice.

The absence of dystrophin in Duchenne muscular dystrophy (DMD) and in the mutant mdx mouse causes muscle degeneration and disruption of the neuromuscular junction. Based on evidence from the denervation-like properties of these muscles, we assessed the ligand-binding constants of nicotinic acetylcholine receptors (nAChRs) and the mRNA expression of individual subunits in membrane preparations of diaphragm muscles from adult (4-month-old) and aged (20-month-old) control and mdx mice. The concentration of nAChRs as determined by the maximal specific [(125)I]-alpha-bungarotoxin binding (Bmax) in the muscle membranes did not change with aging in both animal strains. When compared to age-matched control groups, the Bmax in mdx muscles was increased by 65% in adults, and by 103% in aged mice with no alteration of toxin affinity for nAChRs. Reverse-transcription polymerase chain reaction assays showed that mRNA transcripts for the nAChR alpha1, gamma, alpha7, and beta2, but not the epsilon subunits, were more abundant in mdx than in control muscles. The results indicate increased expression of extrajunctional nAChRs in the mdx diaphragm and reflect impairment of nAChR regulation in dystrophin-deficient muscles. These observations may be related to the resistance to nondepolarizing muscle relaxants and the high sensitivity to depolarizing agents reported in DMD patients.

Bradykinin release and inactivation in brain of rats submitted to an experimental model of Alzheimer's disease.

The kallikrein-kinin system is involved in a variety of physiological and pathological processes. Components of this system, identified in rat and human brains, can be altered in neurodegenerative processes such as Alzheimer's disease. Here, we studied kinin release and its inactivation in rats submitted to chronic cerebroventricular infusion of beta-amyloid (Abeta) peptide. Neurodegeneration was confirmed by histological analysis of brain samples. In cerebrospinal fluid of animals infused with Abeta, bradykinin concentration was increased, as determined by radioimmunoassay. However, in the brain of Abeta group, we only detected the tripeptide Arg-Pro-Pro, purified by reversed-phase chromatography and characterized by liquid chromatography-electrospray ionization mass spectrometry. This fragment of bradykinin indicated the possible participation of kinin-processing enzymes in the brain such as a prolyl oligopeptidase.

Vitamin E prevents cell death induced by mild oxidative stress in chicken skeletal muscle cells.

Apoptosis and necrosis are two forms of cell death that can occur in response to various agents and oxidative damage. In addition to necrosis, apoptosis contributes to muscle fiber loss in various muscular dystrophies as well participates in the exudative diathesis in chicken, pathology caused by dietary deficiency of vitamin E and selenium, which affects muscle tissue. We have used chicken skeletal muscle cells and bovine fibroblasts to study molecular events involved in the cell death induced by oxidative stress and apoptotic agents. The effect of vitamin E on cell death induced by oxidants was also investigated. Treatment of cells with anti-Fas antibody (50 to 400 ng/mL), staurosporine (0.1 to 100 microM) and TNF-alpha (10 and 50 ng/mL) resulted in a little loss of Trypan blue exclusion ability. Those stimuli conducted cells to apoptosis detected by an enhancement in caspase activity upon fluorogenic substrates but this activity was not fully blocked by the caspase inhibitor Z-VAD-fmk. Oxidative stress induced by menadione (10, 100 and 250 muM) promoted a significant reduction in cell viability (10%, 20% and 35% for fibroblasts; 20%, 30% and 75% for muscle cells, respectively) and caused an increase in caspase activity and DNA fragmentation. H2O2 also promoted apoptosis verified by caspase activation and DNA fragmentation, but in higher doses induced necrosis. Vitamin E protected cells from death induced by low doses of oxidants. Although it was ineffective in reducing caspase activity in fibroblasts, this vitamin diminished the enzyme activity in muscle cells. These data suggested that oxidative stress could activate apoptotic mechanisms; however the mode of cell death will depend on the intensity and duration of the stimulus, and on the antioxidant status of the cells.