In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways.

Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders.

Intracardiac Injection of Dental Pulp Stem Cells After Neonatal Hypoxia-Ischemia Prevents Cognitive Deficits in Rats.

Neonatal hypoxia-ischemia (HI) is associated to cognitive and motor impairments and until the moment there is no proven treatment. The underlying neuroprotective mechanisms of stem cells are partially understood and include decrease in excitotoxicity, apoptosis and inflammation suppression. This study was conducted in order to test the effects of intracardiac transplantation of human dental pulp stem cells (hDPSCs) for treating HI damage.

Label-free quantitative proteomics of rat hypothalamus under fever induced by LPS and PGE.

Unlabelled: Fever is a brain-mediated increase in body temperature mainly during inflammatory or infectious challenges. Although there is considerable data regarding the inflammation pathways involved in fever, metabolic alterations necessary to orchestrate the complex inflammatory response are not totally understood. We performed proteomic analysis of rat hypothalamus using label-free LC-MS/MS in a model of fever induced by lipopolysaccharide (LPS) or prostaglandin E (PGE).

Increase of reactive oxygen species in different tissues during lipopolysaccharide-induced fever and antipyresis: an electron paramagnetic resonance study.

Fever is a regulated increase in body temperature and a component of the acute-phase response, triggered mainly after the invasion of pathogens in the body. Reactive oxygen species (ROS) are generated during the physiological and pathological processes, and can act as both signalling molecules as well as promoters of oxidative stress. Male Wistar rats, pretreated with oral doses of acetaminophen, celecoxib, dipyrone, or ibuprofen 30 min before an intravenous lipopolysaccharide (LPS) or sterile saline injection, showed a reduced febrile response in all animals tested.

Chronic Stress Causes Sex-Specific and Structure-Specific Alterations in Mitochondrial Respiratory Chain Activity in Rat Brain.

Chronic restraint stress (CRS) induces a variety of changes in brain function, some of which are mediated by glucocorticoids. The response to stress occurs in a sex-specific way, and may include mitochondrial and synaptic alterations. The synapse is highly dependent on mitochondrial energy supply, and when mitochondria become dysfunctional, they orchestrate cell death.

Sex-dependent consequences of neonatal brain hypoxia-ischemia in the rat.

Neonatal hypoxia-ischemia (HI) is an important cause of neurological deficits in humans, and the Levine-Rice model of experimental HI in the rat mimics the human brain lesion and the following sensory motor deficits and cognitive disabilities. With the growing evidence that sex influences all levels of brain functions, this Mini-Review highlights studies in which sex was a controlled variable and that provided evidence of sexual dimorphism in behavioral outcome, extension of brain damage, mechanisms of lesion, and treatment efficacy in the rat neonatal HI model. It was shown that 1) females have greater memory deficits; 2) cell death is dependent mainly on caspase activation in females; 3) males are more susceptible to oxidative stress; and 4) treatments acting on distinct cell death pathways afford sex-dependent neuroprotection.

Severe Hyperhomocysteinemia Decreases Respiratory Enzyme and Na(+)-K(+) ATPase Activities, and Leads to Mitochondrial Alterations in Rat Amygdala.

Severe hyperhomocysteinemia is caused by increased plasma levels of homocysteine (Hcy), a methionine derivative, and is associated with cerebral disorders. Creatine supplementation has emerged as an adjuvant to protect against neurodegenerative diseases, due to its potential antioxidant role. Here, we examined the effects of severe hyperhomocysteinemia on brain metabolism, and evaluated a possible neuroprotective role of creatine in hyperhomocysteinemia, by concomitant treatment with Hcy and creatine (50 mg/Kg body weight).

Mitochondrial and Oxidative Stress Aspects in Hippocampus of Rats Submitted to Dietary n-3 Polyunsaturated Fatty Acid Deficiency After Exposure to Early Stress.

Chronic dietary long-chain polyunsaturated fatty acids (PUFAs) deficiency may lead to changes in cortex and hippocampus neuronal membrane phospholipids, and may be linked to impaired central nervous system function. Particularly docosahexaenoic acid deficiency appears to be involved in neuropsychiatric disorders. On the other hand, adverse events early in life may also profoundly affect brain development, leading to long-lasting effects on neurophysiology, neurobiology and behavior.

A new device for step-down inhibitory avoidance task--effects of low and high frequency in a novel device for passive inhibitory avoidance task that avoids bioimpedance variations.

Background: Step-down inhibitory avoidance task has been widely used to evaluate aversive memory, but crucial parameters inherent to traditional devices that may influence the behavior analysis (as stimulus frequency, animal's bioimpedance) are frequently neglected.

New Method: We developed a new device for step-down inhibitory avoidance task by modifying the shape and distribution of the stainless steel bars in the box floor where the stimuli are applied. The bars are 2 mm wide, with rectangular shape, arranged in pairs at intervals of 1cm from the next pairs.

Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials.

Materials engineered to elicit targeted cellular responses in regenerative medicine must display bioligands with precise spatial and temporal control. Although materials with temporally regulated presentation of bioadhesive ligands using external triggers, such as light and electric fields, have recently been realized for cells in culture, the impact of in vivo temporal ligand presentation on cell-material responses is unknown. Here, we present a general strategy to temporally and spatially control the in vivo presentation of bioligands using cell-adhesive peptides with a protecting group that can be easily removed via transdermal light exposure to render the peptide fully active.

Dynamic cell-adhesive microenvironments and their effect on myogenic differentiation.

Integrin-mediated cell adhesion plays a central role in cell behavior on biomaterial surfaces and influences various cell functions. Photoactivatable RGD adhesive peptides were used to investigate the effect of the density and time point of bioadhesive ligand presentation on cell adhesion, proliferation and differentiation. PEGylated self-assembled monolayers were functionalized with RGD and caged RGD ligands and seeded with C2C12 myoblasts.

Photoactivatable caged cyclic RGD peptide for triggering integrin binding and cell adhesion to surfaces.

We report the synthesis and properties of a photoactivatable caged RGD peptide and its application for phototriggering integrin- and cell-binding to surfaces. We analysed in detail 1) the differences in the integrin-binding affinity of the caged and uncaged forms by quartz crystal microbalance (QCM) studies, 2) the efficiency and yield of the photolytic uncaging reaction, 3) the biocompatibility of the photolysis by-products and irradiation conditions, 4) the possibility of site, temporal and density control of integrin-binding and therefore human cell attachment, and 5) the possibility of in situ generation of cell patterns and cell gradients by controlling the UV exposure. These studies provide a clear picture of the potential and limitations of caged RGD for integrin-mediated cell adhesion and demonstrate the application of this approach to the control and study of cell interactions and responses.

Neonatal hypoxia-ischemia induces sex-related changes in rat brain mitochondria.

The effects of neonatal hypoxia-ischemia (HI) on energy metabolism in male and female rats were investigated, testing the hypothesis that HI-induced brain mitochondrial dysfunction could present in a dimorphic pattern. Impairment in electron transport chain complex activities at 2 and 18 h after HI was observed in cortex and hippocampus in rats of both sexes, with females presenting an overall activity higher than that of males. Females also showed loss of mitochondrial mass and membrane potential 18 h after HI, while males were only slightly affected.

Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment.

Reduction of cerebral blood flow is an important risk factor for dementia states and other brain dysfunctions. In present study, the effects of permanent occlusion of common carotid arteries (2VO), a well established experimental model of brain ischemia, on memory function were investigated, as assessed by reference and working spatial memory protocols and the object recognition task; cell damage to the hippocampus, as measured through changes in immunoreactivity for GFAP and the neuronal marker NeuN was also studied. The working hypothesis is that metabolic impairment following hypoperfusion will affect neuron and glial function and result in functional damage.

Early biochemical effects after unilateral hypoxia-ischemia in the immature rat brain.

Perinatal hypoxia-ischemia (HI) gives rise to inadequate substrate supply to the brain tissue, resulting in damage to neural cells. Previous studies at different time points of development, and with different animal species, suggest that the HI insult causes oxidative damage and changes Na+, K+-ATPase activity, which is known to be very susceptible to free radical-related lipid peroxidation. The aim of the present study was to establish the onset of the oxidative damage response in neonatal Wistar rats subjected to brain HI, evaluating parameters of oxidative stress, namely nitric oxide production, lipoperoxidation by thiobarbituric acid reactive substances (TBA-RS) production and malondialdehyde (MDA) levels, reactive species production by DCFH oxidation, antioxidant enzymatic activities of catalase, glutathione peroxidase, superoxide dismutase as well as Na+, K+-ATPase activity in hippocampus and cerebral cortex.

Neonatal handling impairs spatial memory and leads to altered nitric oxide production and DNA breaks in a sex specific manner.

Early life events lead to behavioral and neurochemical changes in adulthood. The aim of this study is to verify the effects of neonatal handling on spatial memory, nitric oxide (NO) production, antioxidant enzymatic activities and DNA breaks in the hippocampus of male and female adult rats. Litters of rats were non-handled or handled (10 min/day, days 1-10 after birth).

Diphenyl ditelluride effect on embryo/fetal development in mice: interspecies differences.

It is well established that diphenyl ditelluride, (PhTe)(2), is a potent teratogen in rats, however, little is known about its effects on embryo/fetal development in mice. The present study was undertaken to investigate whether any differences exist on embryo/fetal development of mice exposed to (PhTe)(2) during distinctive periods of gestation compared to rats. Dams were treated subcutaneously (s.

Sub-chronic exposure of adult male rats to diphenyl ditelluride did not affect the development of their progeny.

The present study was undertaken to evaluate the toxicity of diphenyl ditelluride [(PhTe)(2)] exposure on the progeny of Wistar male rats. Male rats were exposed to (PhTe)(2) subcutaneously for 4 weeks (wk) at the dose of 0.006 mg/kg and 8-wk at the dose of 0.

Repeated administration of diphenyl diselenide to pregnant rats induces adverse effects on embryonic/fetal development.

The present study was carried out to investigate the effects of diphenyl diselenide, (PhSe)(2), on embryo-fetal development. Dams were treated subcutaneously with 1.5, 3.

Adult male rats sub-chronically exposed to diphenyl diselenide: Effects on their progeny.

The present study was conducted to evaluate the toxicity of diphenyl diselenide [(PhSe)2] exposure on the progeny of Wistar male rats. Male rats were exposed to (PhSe)2 subcutaneously for 4 weeks at the dose of 5.0 mg/kg and 8 weeks at the dose of 2.

Diphenyl diselenide changes behavior in female pups.

Diphenyl diselenide, (PhSe)(2), is an organoselenium compound that affects a number of neuronal processes. The effect of maternal subcutaneous (s.c.

Sub-chronic administration of diphenyl diselenide potentiates cadmium-induced testicular damage in mice.

Sub-chronic cadmium (Cd) exposure causes testicular damage in mice. The mode of action may involve oxidative stress and especially lipid peroxidation. The present study has monitored the pathogenesis of testicular damage during sub-chronic Cd exposure and has evaluated the potential protective effect of antioxidant therapy with diphenyl diselenide (PhSe)(2).

Assessment of reproductive toxicity in male rats following acute and sub-chronic exposures to diphenyl diselenide and diphenyl ditelluride.

The present study was conducted to evaluate the toxicity of the exposure to diphenyl diselenide [(PhSe)2] and diphenyl ditelluride [(PhTe)2] on reproductive system in Wistar rats. Adult male rats were exposed intraperitonealy (acute) or subcutaneously (sub-chronic, during 4 or 8 weeks) to (PhSe)2 or (PhTe)2 prior to mating. A number of biochemical parameters in rat testes were examined, such as delta-aminolevulinate dehydratase (delta-ALA-D) activity, lipid peroxidation, glycogen content and components of the antioxidant defenses (superoxide dismutase (SOD) activity and ascorbic acid concentration).

Teratogenic effects of diphenyl diselenide in Wistar rats.

Diphenyl diselenide is an organoselenium compound with potential therapeutic use. The present study evaluates the effects of single maternal subcutaneous injection of 50 and 100mg/kg diphenyl diselenide [(PhSe)2] at gestational days (GD) 6, 10 or 17 in Wistar rats. The highest dose of (PhSe2 was also administered at GD 7-12.