Prenatal stress exerts a strong impact on fetal brain development in rats impairing adaptation to stressful conditions, subsequent vulnerability to anxiety, altered sexual function, and enhanced propensity to self-administer drugs. Most of these alterations have been attributed to changes in the neurotransmitter dopamine (DA). In humans; dysfunction of dopaminergic system is associated with development of several neurological disorders, such as Parkinson disease, schizophrenia, attention-deficit hyperactivity disorder, and depression. Evidences provided by animal research, as well as retrospective studies in humans, pointed out that exposure to adverse events in early life can alter adult behaviors and neurochemical indicators of midbrain DA activity, suggesting that the development of the DA system is sensitive to disruption by exposure to early stressors. The purpose of this article is to provide a general overview of published studies and our own study related to the effect of prenatal insults on the development of DA metabolism and biology, focusing mainly in articles involving prenatal-restraint stress protocols in rats. We will also attempt to make a correlation between theses alterations and DA-related pathological processes in humans.

Permanent metal implants are widely used in human medical treatments and orthopedics, for example as hip joint replacements. They are commonly made of titanium alloys and beyond the optimization of this established material, it is also essential to explore alternative implant materials in view of improved osseointegration. The aim of our study was to characterize the implant performance of zirconium in comparison to titanium implants. Zirconium implants have been characterized in a previous study concerning material properties and surface characteristics in vitro, such as oxide layer thickness and surface roughness. In the present study, we compare bone material quality around zirconium and titanium implants in terms of osseointegration and therefore characterized bone material properties in a rat model using a multi-method approach. We used light and electron microscopy, micro Raman spectroscopy, micro X-ray fluorescence and X-ray scattering techniques to investigate the osseointegration in terms of compositional and structural properties of the newly formed bone. Regarding the mineralization level, the mineral composition, and the alignment and order of the mineral particles, our results show that the maturity of the newly formed bone after 8 weeks of implantation is already very high. In conclusion, the bone material quality obtained for zirconium implants is at least as good as for titanium. It seems that the zirconium implants can be a good candidate for using as permanent metal prosthesis for orthopedic treatments.

The development of the central nervous system can be permanently affected by insults received during the perinatal period, predisposing the organism to long-term behavioral and neurochemical abnormalities. Rats exposed to different types of stress during the last week of gestation produce offspring that show several alterations, many of which have been attributed to changes in dopamine (DA) neurotransmission that could serve as the neurochemical basis for the development of neuropsychiatric disorders. Employing an immunocytochemical approach, we studied the expression levels of two transcription factors Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation as well as the expression of the rate limiting enzyme in DA synthesis, tyrosine hydroxylase (TH) in mesencephalic areas of the brains of prenatally stressed (PS) offspring at different postnatal ages. Main results show that stress exerted to the gestant mother produces permanent effect in the ontogenetic expression of key factors related to the DA metabolism mainly in the ventral tegmental area (VTA) of the mesencephalon. The immunocytochemical expression of the transcription factor Nurr1 shows an increase at postnatal days (PNDs) 7, 28, and 60 whereas Pitx3 shows a decrease at PND 28 and an increase at 60 PND. The rate limiting step in DA synthesis, the enzyme TH shows a decrease at PND 7 to reach control levels at PNDs 28 and 60. The increase of TFs might be up-regulating TH in order to restore DA levels that were previously seen to be normal before puberty. The area selectivity of the increase of the TFs toward VTA and the mesolimbic pathway indicates that an insult received during the prenatal period will exert mainly motivational, emotional, and reward behavior impairments in the adult life.

No abstract

Rats exposed to different types of stress during the last week of pregnancy produce offspring that show severe anomalies in neural development and brain morphology. We have previously reported that prenatal stress (PS) induced by immobilization increases D2-type dopamine (DA) receptor levels in the adult offspring, with a concomitant reduction in DA release in prefrontal cortex after amphetamine stimulation. Recently, two transcription factors, Nurr1 and Pitx3, have been identified that are expressed at critical moments of DA neuron differentiation. Their genetic expression is activated immediately after these neuron determinations and maintained through adult life. Nurr1 regulates several proteins that are required for dopamine synthesis and regulation, and Pitx3 is specifically involved in the terminal differentiation and maintenance of dopamine neurons. By means of an immunocytochemistry approach, we studied the expression of Nurr1 and found an ubiquitous distribution in cerebral cortex, hippocampus, thalamus, amygdala, and midbrain, whereas Pitx3 remains restricted to the mesencephalic DA neurons such as substantia nigra and ventral tegmental area. Our results show that the expression of both Nurr1 and Pitx3 increased in prenatally stressed adult offspring in the ventral tegmental area, whereas no changes were observed in the substantia nigra area. It might be hypothesized that the increase of the specific dopaminergic transcription factors might be a compensatory mechanism to counteract the reduction in dopamine levels previously observed as a consequence of prenatal stress.

No abstract

The mechanical properties and good biocompatibility of zirconium and some of its alloys make these materials good candidates for biomedical applications. The attractive in vivo performance of zirconium is mainly due to the presence of a protective oxide layer. In this preliminary study, the surface of pure zirconium modified by anodisation in acidic media at low potentials to enhance its barrier protection given by the oxides and osseointegration. Bare, commercially pure zirconium cylinders were compared to samples anodised at 30 V through electrochemical tests and scanning electron microscopy (SEM). For both conditions, in vivo tests were performed in a rat tibial osteotomy model. The histological features and fluorochrome-labelling changes of newly bone formed around the implants were evaluated on the non-decalcified sections 63 days after surgery. Electrochemical tests and SEM images show that the anodisation treatment increases the barrier effect over the material and the in vivo tests show continuous newly formed bone around the implant with a different amount of osteocytes in their lacunae depending on the region. There was no significant change in bone thickness around either kind of implant but the anodised samples had a significantly higher mineral apposition, suggesting that the anodisation treatment stimulates and assists the osseointegration process. We conclude that anodisation treatment at 30 V can stimulate the implant fixation in a rat model, making zirconium a strong candidate material for permanent implants.

Exposure to a variety of stressful events during the last week of pregnancy in rats interferes with the correct progeny development, which in turn leads to delays in motor development, impaired adaptation to stressful conditions, altered sexual behaviour, learning deficits, neuronal development and brain morphology. Many of these alterations have been attributed to changes in dopamine (DA) neurotransmission and occur primarily in the mesolimbic system. We found that prenatally stressed offspring showed higher levels of cells expressing tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and that these cells were more susceptible to a neurochemical insult with 6-hydroxy-DA (6-OHDA) in adulthood. Moreover, prenatally stressed rats presented differences in terms of the number and asymmetry of neuronal nitric oxide synthase-expressing cells in the VTA and nucleus accumbens, respectively. Similar to the results described for TH-expressing cells, the nitrergic systems were differentially regulated after 6-OHDA lesion in control and prenatally stressed rats. These results indicated that prenatal stress affects the dopaminergic and nitrergic systems in the mesolimbic pathway. In addition, we propose that the mesolimbic areas are more susceptible than the motor areas to a neurochemical insult during adult life.