Delayed physical and neurobehavioral development and increased aggressive and depression-like behaviors in the rat offspring of dams fed a high-fat diet

Early maternal exposure to a high-fat diet (HFD) may influence the brain development of rat offspring and consequently affect physiology and behavior. Thus, in the present study, we investigated the somatic, physical, sensory-motor and neurobehavioral development of the offspring of dams fed an HFD (52% calories from fat, mainly saturated) and the offspring of dams fed a control diet (CD – 14.7% fat) during lactation from the 1st to the 21st postnatal day (P). Maternal body weights were evaluated during lactation. In the progeny, somatic (body weight, head and lengths axes) and physical (ear unfolding, auditory conduit opening, eruption of the incisors and eye opening) development and the consolidation of reflex responses (palm grasp, righting, vibrissa placing, cliff avoidance, negative geotaxis, auditory startle response and free-fall righting) were determined during suckling. Depressive and aggressive behaviors were tested with the forced swimming test (FST) and the “foot-shock” test on days 60 and 110, respectively. The open field test was used to assess motor function. Compared to controls, the HFD-pups exhibited decreases in body weight (P7–P21) and body length (P4–P18), but by days P71 and P95, these pups were overweight. All indicators of physical maturation and the consolidation of the following reflexes, vibrissa placing, auditory startle responses, free-fall righting and negative geotaxis, were delayed in HFD-progeny. In addition, the pups from HFD dam rats also exhibited reduced swimming and climbing times in the FST and increased aggressive behavior. No changes in locomotion were observed. These findings show developmental and neurobehavioral changes in the rat offspring of dams fed the HFD during lactation and suggest possible disruption of physical and sensory-motor maturation and increased susceptibility to depressive and aggressive-like behavior.     

Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid

The influence of acute renal failure induced by gentamicin administration on the effects of MMA on mitochondrial respiratory chain complexes, citrate synthase, succinate dehydrogenase and creatine kinase activities in cerebral cortex and kidney of young rats were investigated. Animals received one intraperitoneal injection of saline or gentamicin (70 mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67 μmol/g) or saline (11 h interval between injections) and 60 min after the last injection the animals were killed. Acute MMA administration decreased creatine kinase activity in both tissues and increased complexes I–III activity in cerebral cortex. Creatine kinase activity was also inhibited by gentamicin administration. Simultaneous administration of MMA and gentamicin increased the activities of citrate synthase in cerebral cortex and kidney and complexes II–III in cerebral cortex. The other enzyme activities in cerebral cortex and kidney of animals receiving MMA plus gentamicin did not significantly differ from those observed in animals receiving only MMA. Our present data is line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on the Krebs cycle and respiratory chain in brain and peripheral tissues.     

First-generation neuronal precursors in the crayfish brain are not self-renewing

Adult-born neurons in crayfish (Procambarus clarkii) are the progeny of 1st-generation precursor cells (functionally analogous to neuronal stem cells in vertebrates) that are located in a neurogenic niche on the ventral surface of the brain. The daughters of these precursor cells migrate along the processes of bipolar niche cells to proliferation zones in the cell clusters where the somata of the olfactory interneurons reside. Here they divide again, producing offspring that differentiate into olfactory local and projection neurons. The features of this neuronal assembly line, and the fact that it continues to function when the brain is isolated and perfused or maintained in organotypic culture, provide opportunities unavailable in other organisms to explore the sequence of cellular and molecular events leading to the production of new neurons in adult brains. Further, we have determined that the 1st-generation precursor cells are not a self-renewing population, and that the niche is, nevertheless, not depleted as the animals grow and age. We conclude, therefore, that the niche is not a closed system and that there must be an extrinsic source of neuronal stem cells. Based on in vitro studies demonstrating that cells extracted from the hemolymph are attracted to the niche, as well as the intimate relationship between the niche and vasculature, we hypothesize that the hematopoietic system is a likely source of these cells.     

NTPDase and 5′-nucleotidase activities from synaptosomes and platelets of rats exposed to cadmium and treated with N-acetylcysteine

The purpose of the present investigation was to evaluate the hydrolysis of adenine nucleotides on synaptosomes and platelets obtained from rats exposed to cadmium (Cd) and treated with N-acetylcysteine (NAC). Rats received Cd (2 mg/kg) and NAC (150 mg/kg) by gavage every other day for 30 days. Animals were divided into four groups (n = 4–6): control/saline, NAC, Cd, and Cd/NAC. The results of this study demonstrated that NTPDase and 5′-nucleotidase activities were increased in the cerebral cortex synaptosomes of Cd-poisoned rats, and NAC co-treatment reversed these activities to the control levels. In relation to hippocampus synaptosomes, no differences on the NTPDase and 5′-nucleotidase activities of Cd-poisoned rats were observed and only the 5′-nucleotidase activity was increased by the administration of NAC per se. In platelets, Cd-intoxicated rats showed a decreased NTPDase activity and no difference in the 5′-nucleotidase activity; NAC co-treatment was inefficient in counteracting this undesirable effect. Our findings reveal that adenine nucleotide hydrolysis in synaptosomes and platelets of rats were altered after Cd exposure leading to a compensatory response in the central nervous system and acting as a modulator of the platelet activity. NAC was able to modulate the purinergic system which is interesting since the regulation of these enzymes could have potential therapeutic importance. Thus, our results reinforce the importance of the study of the ecto-nucleotidases pathway in poisoning conditions and highlight the possibility of using antioxidants such as NAC as adjuvant against toxicological conditions.     

Parkin-Knockout Mice did not Display Increased Vulnerability to Intranasal Administration of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

The loss of nigral dopaminergic neurons in Parkinson’s disease (PD) is believed to result from interactions between genetic susceptibility and environmental factors. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, the hybrid 129Sv-C57BL/6 parkin-deficient mice did not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to neurotoxicity induced by 6-hydroxydopamine (6-OHDA) or intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. We aimed to re-evaluate the role of parkin in a pure C57BL/6 background after an acute intranasal (i.n.) MPTP administration, a new route of toxin delivery to the brain that mimics environmental exposure to neurotoxins. We found that the deficiency of parkin gene modifies the d-amphetamine-induced locomotion in saline-treated animals. Intranasal MPTP induced Parkinsonism in parkin^+/+ mice, through depletion of striatal dopamine, decreased number of dopaminergic neurons in the substantia nigra, and decreased d-amphetamine-induced hyperlocomotion. Additionally, the deletion of the parkin gene in a pure C57BL/6 background did not lead to increased vulnerability to i.n. MPTP-induced neurotoxicity. Moreover, the i.n. MPTP induced nigral astrogliosis predominantly in the pars reticulata in wild type and parkin^?/? mice. Taken together, these results showed that the absence of parkin did not modify the vulnerability of nigrostriatal dopaminergic pathway after i.n. MPTP intoxication, suggesting that independently of mouse strain, the endogenous parkin is not required for protection of this system. These findings also suggest that the development of familial parkin-linked PD is not associated with exposure to environmental factors that specifically affects the dopaminergic system.     

Posterior Reversible Encephalopathy Syndrome Following a Scorpion Sting

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity not yet understood, that is present with transient neurologic symptoms and particular radiological findings. The most common imaging pattern in PRES is the presence of edema in the white matter of the posterior portions of both cerebral hemispheres. The cause of PRES is unclear. We report a case of 13‐year‐old male who was stung by a scorpion and developed a severe headche, visual disturbance, and seizures and had the diagnosis of PRES with a good outcome. Numerous factors can trigger this syndrome, most commonly: acute elevation of blood pressure, abnormal renal function, and immunosuppressive therapy. There are many cases described showing the relationship between PRES and eclampsia, transplantation, neoplasia and chemotherapy treatment, systemic infections, renal disease acute, or chronic. However, this is the first case of PRES following a scorpion sting.     

Trends in prevalence and characteristics of post-neonatal cerebral palsy cases: A European registry-based study

The present paper aims to analyze trends over time in prevalence of cerebral palsy of post-neonatal origin, to investigate whether changes are similar according to severity and to describe the disability profile by etiology. Post-neonatal cases, birth years 1976 to 1998, were identified from the Surveillance of Cerebral Palsy in Europe collaboration (19 population-based registries). A recognized causal event occurring between 28 days and 24 months of age was considered to define the cases. Trends in prevalence were explored using graphical methods (Lowess and Cusum control chart) and modeled with negative binomial regressions. Over the study period, 404 cases were identified as post-neonatal cases (5.5% of the total). Mean prevalence rate was 1.20 per 10,000 live births (95% CI [1.08–1.31]). A significant downward trend was observed (p = 0.001), with an accentuated decrease in the 1990s. The prevalence of severe cases which account for around one third of the total also significantly decreased over time (p < 0.001). In 46% of cases, an infectious aetiology was reported; the corresponding prevalence significantly decreased since 1989. No significant decrease was observed for the rate of cases due to a vascular episode or of traumatic origin. Our results emphasize the need of large population-based surveillance systems to reliably monitor trends in prevalence in rare subgroups of children like those with acquired cerebral palsy. The decrease of the overall prevalence as well as those of the most severe cases may be partly due to public health actions targeted to prevent such events.