Long-Term Methionine Exposure Induces Memory Impairment on Inhibitory Avoidance Task and Alters Acetylcholinesterase Activity and Expression in Zebrafish (Danio rerio)

Hypermethioninemic patients exhibit a variable degree of neurological dysfunction. However, the mechanisms involved in these alterations have not been completely clarified. Cholinergic system has been implicated in many physiological processes, including cognitive performances, as learning, and memory. Parameters of cholinergic signaling have already been characterized in zebrafish brain. Since zebrafish is a small freshwater teleost which is a vertebrate model for modeling behavioral and functional parameters related to human pathogenesis and for clinical treatment screenings, in the present study we investigated the effects of short- and long-term methionine exposure on cognitive impairment, AChE activity and gene expression in zebrafish. For the studies, animals were exposed at two methionine concentrations (1.5 and 3.0 mM) during 1 h or 7 days (short- or long-term treatments, respectively). We observed a significant increase in AChE activity of zebrafish brain membranes after long-term methionine exposure at 3.0 mM. However, AChE gene expression decreased significantly in both concentrations tested after 7 days of treatment, suggesting that post-translational events are involved in the enhancement of AChE activity. Methionine treatment induces memory deficit in zebrafish after long-term exposure to this amino acid, which could be related, at least in part, with cognitive impairment observed in hypermethioninemia. Therefore, the results here presented raise a new perspective to use the zebrafish as a complementary vertebrate model for studying inborn errors of metabolism, which may help to better understand the pathophysiology of this disease.     

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10 mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β₁ (TGF-β₁) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β₁, as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β₁ and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.     

Detection of human herpesvirus 7 infection in young children presenting with exanthema subitum

In this study, we assessed the prevalence of human herpesvirus-7 (HHV-7) in 141 serum samples from children less than four years of age with exanthematic disease. All samples were negative for measles, rubella, dengue fever and parvovirus B19 infection. Testing for the presence of human herpesvirus-6 (HHV-6)-specific high avidity IgG antibodies by indirect immunofluorescence assay (IFA) revealed two main groups: one composed of 57 patients with recent primary HHV-6 infection and another group of 68 patients showing signs of past HHV-6 infection. Another 16 samples had indeterminate primary HHV-6 infection, by both IgG IFA and IgM IFA. Serum samples were subjected to a nested polymerase chain reaction to detect the presence of HHV-7 DNA. Among patients with a recent primary HHV-6 infection, HHV-7 DNA was present in 1.7% of individuals; however, 5.8% of individuals tested positive for HHV-7 DNA in the group with past primary HHV-6 infection. Among the 16 samples with indeterminate diagnosis, 25% (4/16) had HHV-7 DNA (p < 0.002). We hypothesise that HHV-7 might be the agent that causes exanthema. However, a relationship between clinical manifestations and the detection of virus DNA does not always exist. Therefore, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease. In conclusion, we detected HHV-7 DNA in young children from the state of Rio de Janeiro, Brazil.     

Alpha-tocopherol protects against memory impairment caused by L-NAME and modulates the injury marker and blood coagulant parameters

Cerebrovascular disease studies have shown similarity between humans and spontaneously hypertensive rats stroke-prone rats in the development of spontaneous stroke and transitory ischemic attacks (TIA). In addition, nitric oxide (NO) suppression by L-arginine methyl ester (L-NAME) can precipitate several vascular diseases including TIA and strokes. On the other hand, alpha-tocopherol (AT) has been associated with beneficial effects on vascular disorders. Four groups were tested to evaluate AT effects on NO inhibition: AT, control (C), AT + L-NAME, and L-NAME. During 4 weeks, all groups had their physiologic parameters evaluated and were submitted to neurological tests. After the sacrifice of the animals, total L-lactate dehydrogenase, fibrinogen levels, and platelet counts were measured. Our results demonstrated improvement in memory function and sensory-motor function of the rats treated with AT. The AT treatment also demonstrated a significant difference on the injury identifier, fibrinogen levels, and platelet count between the treated groups and the L-NAME group. In conclusion, AT reversed damaging L-NAME neurological effects and could be considered as a possible protective agent in neurological diseases.     

SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance

Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin. Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity. Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.     

Have Historical Climate Changes Affected Gentoo Penguin (Pygoscelis papua) Populations in Antarctica?

The West Antarctic Peninsula (WAP) has been suffering an increase in its atmospheric temperature during the last 50 years, mainly associated with global warming. This increment of temperature trend associated with changes in sea-ice dynamics has an impact on organisms, affecting their phenology, physiology and distribution range. For instance, rapid demographic changes in Pygoscelis penguins have been reported over the last 50 years in WAP, resulting in population expansion of sub-Antarctic Gentoo penguin (P. papua) and retreat of Antarctic Adelie penguin (P. adeliae). Current global warming has been mainly associated with human activities; however these climate trends are framed in a historical context of climate changes, particularly during the Pleistocene, characterized by an alternation between glacial and interglacial periods. During the last maximal glacial (LGM∼21,000 BP) the ice sheet cover reached its maximum extension on the West Antarctic Peninsula (WAP), causing local extinction of Antarctic taxa, migration to lower latitudes and/or survival in glacial refugia. We studied the HRVI of mtDNA and the nuclear intron βfibint7 of 150 individuals of the WAP to understand the demographic history and population structure of P. papua. We found high genetic diversity, reduced population genetic structure and a signature of population expansion estimated around 13,000 BP, much before the first paleocolony fossil records (∼1,100 BP). Our results suggest that the species may have survived in peri-Antarctic refugia such as South Georgia and North Sandwich islands and recolonized the Antarctic Peninsula and South Shetland Islands after the ice sheet retreat.     

A new occurrence of Limnoperna fortunei (Dunker 1856) (Bivalvia, Mytilidae) in the State of S?o Paulo, Brazil.

The freshwater mussel Limnoperna fortunei (Dunker 1856) (Bivalvia, Mytilidae) has been found in the Paraná river, near Rosana, S?o Paulo. This is the first record of this specie in S?o Paulo State. This population of Limnoperna fortunei seems to be young and in a colonization process.