Highlights ► Carotids were occluded with 1 week interval in the modified two-vessel occlusion. ► Modified 2VO causes long-term memory impairment. ► Neuronal damage and reactive astrogliosis happens ...in the acute phase. ► Cognitive behavior installed in stages more chronic of the model.
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. Seven-day-old Wistar rats were divided into four groups: sham-saline, sham-hDPSCs, HI-saline, and HI-hDPSCs. Motor and cognitive tasks were performed from postnatal day 30. HI-induced cognitive deficits in the novel-object recognition test and in spatial reference memory impairment which were prevented by hDPSCs. No motor impairments were observed in HI animals. Immunofluorescence analysis showed human-positive nuclei in hDPSC-treated animals closely associated with anti-GFAP staining in the lesion scar tissue, suggesting that these cells were able to migrate to the injury site and could be providing support to CNS cells. Our study evidence novel evidence that hDPSC can contribute to the recovery following hypoxia-ischemia and highlight the need of further investigation in order to better understand the exact mechanisms underlying its neuroprotective effects.
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. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.
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.
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. Each pair makes an electrical dipole where the polarity inverts after each pulse. This device also presents a component that acquires and records the exact current received by the animal foot and precisely controls the frequency of stimulus applied during the entire experiment.
Different from conventional devices, this new apparatus increases the contact surface with bars and animal's paws, allowing the electric current pass through the animal's paws only, drastically reducing the influence of animal's bioimpedance. The analysis of recorded data showed that the current received by the animal was practically the same as applied, independent of the animal's body composition. Importantly, the aversive memory was observed at specific stimuli intensity and frequency (0.35 or 0.5 mA at 62 and 125 Hz but not at 0.20 mA or 20 Hz). Moreover, with this device it was possible to observe the well-known step-down inhibitory avoidance task memory impairment induced by guanosine.
This new device offers a substantial improvement for behavioral analysis in step-down inhibitory avoidance task and allows us to precisely compare data from different animals with distinct body composition.
Aluminum is one of the most abundant elements on the planet. The effects of its toxicity to plants include inhibition of the growth of the root system and inhibition of enzymes of plant metabolism ...causing a delay in development. The objective of the present study was to analyze the effects of aluminum on the activity of the enzyme δ-aminolevulinic acid dehydratase (ALA-D), responsible for the formation of the monopyrrole porphobilinogen that is part of the chlorophyll molecule, as well as the cytochromes, in cucumbers. Plant growth was also monitored and the roots were submitted to histological analysis. The concentrations of Al
2(SO
4)
3 used in the growth medium ranged from 1 to 2000
μmol/L. Cucumber (
Cucumis sativus) was chosen because it is a good bioindicator of metal pollution. Results demonstrated that aluminum inhibits this enzyme and also greatly impairs plant growth. Histological analysis of the roots indicated a delay in the development of the vase elements, alterations in cell shape and cellular lesions. ALA-D inhibition may be due to the fact that aluminum present in the growth medium can compete with Mg
2+ or reduce the expression of ALA-D. Probably, Al
3+ forms complexes with nucleotides, with the cell wall and with other biomolecules, reducing the growth and development of the plant.
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. This study aimed to investigate the CRS effects on mitochondrial respiratory chain activity, as well as mitochondrial potential and mass in cell body and synapses using hippocampus, cortex and striatum of male and female rats. Rats were divided into non-stressed (control) and stressed group (CRS during 40 days). Results showed that CRS increased complex I–III activity in hippocampus. We also observed an interaction between CRS and sex in the striatal complex II activity, since CRS induced a reduction in complex II activity in males, while in females this activity was increased. Also an interaction was observed between stress and sex in cortical complex IV activity, since CRS induced increased activity in females, while it was reduced in males. Glucocorticoid receptor (GR) content in cortex and hippocampus was sexually dimorphic, with female rats presenting higher levels compared to males. No changes were observed in GR content, mitochondrial potential or mass of animals submitted to CRS. It was concluded that CRS induced changes in respiratory chain complex activities, and some of these changes are sex-dependent: these activities are increased in the striatal mitochondria by CRS protocol mainly in females, while in males it is decreased.
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 δ-aminolevulinate dehydratase (δ-ALA-D) activity, lipid peroxidation, glycogen content and components of the antioxidant defenses (superoxide dismutase (SOD) activity and ascorbic acid concentration). Furthermore, a possible effect on fertility and reproductive performance in male rats were studied. Sperm counts of caudal epididymis were also evaluated. No lethality was noted in any group. Reduction on body weight in rats which received (PhTe)
2 was only evidenced in acute exposure, while (PhSe)
2-exposed rats presented significant loss of body weight in acute and 4
week-exposure. Mating and fertility indexes were not affected after acute and sub-chronic exposure. Regarding other parameters studied, except for a decrease in testes glycogen content in acutely (PhSe)
2-treated group, no alterations were found in treated groups. Sperm counts of rats treated acutely and sub-chronically were unaffected by drugs exposure. Histological evaluation revealed no modification on testicular tissue in rats exposed to (PhSe)
2 and (PhTe)
2. The results suggest the absence of the male reproductive toxicity induced by (PhSe)
2 and (PhTe)
2 administered intraperitonealy (acute) or subcutaneously (sub-chronical) to adult rats Wistar.
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 2.5
mg/kg, prior to mating with unexposed females. No lethality was noted in any group. At term of exposure period, 4-week exposed male rats presented significant decrease in the body weight. Sex organ weights were similar in (PhSe)
2-exposed and control male groups. The number of implantation sites in females mated with males exposed to (PhSe)
2 for 8 weeks was significantly higher than those of the respective control group. Male exposure to (PhSe)
2, administered for 4 and 8 weeks, did not change fetal body weight. Gross examination of fetuses from 4- to 8-week exposed groups did not reveal the appearance of external anomalies. Examination of live fetuses for ossification centers did not show significantly difference between groups. No increase in the incidence of skeletal anomalies was observed in fetuses obtained from females impregnated with (PhSe)
2-exposed males. The current study indicated that (PhSe)
2 given sub-chronically (4 or 8 weeks) to male rats had no adverse effects on 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 0.003
mg/kg, prior to mating with unexposed females. The body and sex organ weights of male rats were not affected in both 4- and 8-wk (PhTe)
2-exposed groups. The gravid uterus weight and the body weight gain (overall or corrected) during the pregnancy were not statistically different to those obtained from females mated with control males. The number of implantation sites, resorptions and live and dead fetuses were not affected by male exposure to (PhTe)
2. Fetal body weight and crown-rump length were not affected, as well. Examination of the fetuses from both exposed groups for external and skeletal changes did not reveal any male-mediated effect of (PhTe)
2. The current study indicated that (PhTe)
2 given sub-chronically (4- or 8-wk) to male rats had no adverse effects on their progeny.
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