Glyphosate-induced glioblastoma cell proliferation: Unraveling the interplay of oxidative, inflammatory, proliferative, and survival signaling pathways.

The aim of the present study was to investigate the impacts of glyphosate herbicide on the survival and proliferation of glioblastoma cells and to explore the molecular mechanisms underlying such effects. For this, cultured human glioblastoma cell line, A172, was exposed to the glyphosate analytical standard, a glyphosate-based herbicide formulation (GBH), or the metabolite aminomethylphosphonic acid (AMPA). The three compounds induced A172 cytotoxicity after 24 h of exposure, with more prominent cytotoxic effects after 48 and 72 h of treatment. Further experiments were performed by treating A172 cells for 6 h with glyphosate, GBH, or AMPA at 0.5 mg/L, which corresponds to the maximum residue limits for glyphosate and AMPA in drinking water in Brazil. Colony forming units (CFU) assay showed that AMPA increased the number of CFU formed, while glyphosate and GBH increased the CFU sizes. The three compounds tested altered the cell cycle and caused DNA damage, as indicated by the increase in γ-H2AX. The mechanisms underlying the pesticide effects involve the activation of Akt and mitogen-activated protein kinases (MAPKs) signaling pathways, oxidative imbalance, and inflammation. Glyphosate led to NLRP3 activation culminating in caspase-1 recruitment, while AMPA decreased NLRP3 immunocontent and GBH did not alter this pathway. Results of the present study suggest that exposure to glyphosate (isolated or in formulation) or to its metabolite AMPA may affect cell signaling pathways resulting in oxidative damage and inflammation, giving glioblastoma cells an advantage by increasing their proliferation and growth.

Effects of postnatal ethanol exposure and maternal separation on mood, cognition and hippocampal arborization in adolescent rats.

Ethanol exposure and early life stress during brain development are associated with an increased risk of developing psychiatric disorders. We used a third-trimester equivalent model of fetal alcohol spectrum disorders combined with a maternal separation (MS) protocol to evaluate whether these stressors cause sexually dimorphic behavioral and hippocampal dendritic arborization responses in adolescent rats. Wistar rat pups were divided into four experimental groups: 1) Control; 2) MS (MS, for 3 h/day from postnatal (PND) 2 to PND14); 3) EtOH (EtOH, 5 g/kg/day, i.p., PND2, 4, 6, 8, and 10); 4) EtOH + MS. All animals were divided into two cohorts and subjected to a battery of behavioral tests when they reached adolescence (PND37-44). Animals from cohort 1 were submitted to: 1) the open field test; 2) self-cleaning behavior (PND38); and 3) the motivation test (PND39-41). Animals from cohort 2 were submitted to: 1) the novel object recognition (PND37-39); 2) social investigation test (PND40); and 3) Morris water maze test (PND41-44). At PND45, the animals were euthanized, and the brains were collected for subsequent dendritic analysis. Postnatal ethanol exposure (PEE) caused anxiety-like behavior in females and reduced motivation, and increased hippocampal dendritic arborization in both sexes. MS reduced body weight, increased locomotor activity in females, and increased motivation, and hippocampal dendritic arborization in both sexes. We found that males from the EtOH + MS groups are more socially engaged than females, who were more interested in sweets than males. Altogether, these data suggest that early life adverse conditions may alter behavior in a sex-dependent manner in adolescent rats.

Saneamento básico inadequado impacta no desenvolvimento infantil / Inadequate sanitation impacts child development

O objetivo desta pesquisa foi avaliar o desenvolvimento motor de pré-escolares, associando o impacto das condições socioambientais no desenvolvimento motor. Foram avaliadas 342 crianças entre três e quatro anos de idade (36 a 57 meses) de duas regiões distintas: 203 escolares em uma cidade do sul do Brasil e 139 em um município nordestino. O protocolo utilizado para identificar as disfunções motoras (dispraxias) nas áreas da coordenação (fina e global); propriocepção (equilíbrio e esquema corporal); e percepção (organização espacial e temporal) foi a Escala de Desenvolvimento Motor ­ EDM. Os dados relacionados ao saneamento básico foram extraídos de documentos oficiais reconhecidos nacionalmente. Foram encontradas diferenças significativas no desenvolvimento das crianças entre os dois municípios. Os resultados mostram maior prevalência de transtornos motores no município do nordeste, totalizando 40 crianças (28,8%); enquanto no Sul, 26 crianças (12,8%) apresentaram déficits. Todos os dados que se referem ao saneamento básico e índices sociais, encontrados na literatura específica, foram inferiores na cidade nordestina quando comparados ao município da região sul. O presente estudo mostra que carências nas condições socioambientais podem impactar negativamente o desenvolvimento motor de pré-escolares, aumentando a prevalência das dispraxias.

The aim of this research was to assess the motor development in preschoolers, associating the impact of socio-environmental conditions in motor development. A total of 342 children between the ages of 3 and 4 years (36 to 57 months) from two distinct parts of Brazil participated in the study: 203 from a city in the south of Brazil and 139 in a northeast city. The tool used to identify motor dysfunction (dyspraxia) in motor coordination (fine and global), proprioception (balance and body scheme), and perception (spatial and temporal organization) was the Motor Development Scale - MDS. Data related to basic sanitation were extracted from official documents. Significant differences were found between children in the two cities. Results show a higher prevalence of motor dysfunction in the northeast city (total of 40 children - 28.8%), while in the south, 26 children (12.8%) had deficits. All data referring to basic sanitation and social indexes, found in the specific literature, were lower in the northeastern city when compared to the city of the southern region. The present study shows that deficiencies in social and environmental conditions can negatively impact motor development of preschoolers, increasing the prevalence of dyspraxia.

Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice for Huntington's Disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in the HD gene, resulting in an extended polyglutamine tract in the protein huntingtin. HD is traditionally viewed as a movement disorder, but cognitive and neuropsychiatric symptoms also contribute to the clinical presentation. Depression is one of the most common psychiatric disturbances in HD, present even before manifestation of motor symptoms. Diagnosis and treatment of depression in HD-affected individuals are essential aspects of clinical management in this population, especially owing to the high risk of suicide. This study investigated whether chronic administration of the antioxidant probucol improved motor and affective symptoms as well as hippocampal neurogenic function in the YAC128 transgenic mouse model of HD during the early- to mild-symptomatic stages of disease progression. The motor performance and affective symptoms were monitored using well-validated behavioral tests in YAC128 mice and age-matched wild-type littermates at 2, 4, and 6 months of age, after 1, 3, or 5 months of treatment with probucol (30 mg/kg/day via water supplementation, starting on postnatal day 30). Endogenous markers were used to assess the effect of probucol on cell proliferation (Ki-67 and proliferation cell nuclear antigen (PCNA)) and neuronal differentiation (doublecortin (DCX)) in the hippocampal dentate gyrus (DG). Chronic treatment with probucol reduced the occurrence of depressive-like behaviors in early- and mild-symptomatic YAC128 mice. Functional improvements were not accompanied by increased progenitor cell proliferation and neuronal differentiation. Our findings provide evidence that administration of probucol may be of clinical benefit in the management of early- to mild-symptomatic HD.