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Supplemental material, Supplementary_Material for Sex influences in the preventive effects of N-acetylcysteine in a two-hit animal model of schizophrenia by Aline Santos Monte, Francisco Eliclécio Rodrigues da Silva, Camila Nayane de Carvalho Lima, Germana Silva Vasconcelos, Nayana Soares Gomes, Fábio Miyajima, Silvania Maria Mendes Vasconcelos, Clarissa S Gama, Mary V Seeman, David Freitas de Lucena and Danielle S Macedo in Journal of Psychopharmacology

Early-life challenges, particularly infections and stress, are related to neuropsychiatric disorders such as autism and schizophrenia. Here, we conducted a wide range of behavioral tests in periadolescent (postnatal day (PN) 35) and adult (PN70) Swiss mice neonatally challenged with LPS on PN5 and -7, to unveil behavioral alterations triggered by LPS exposure. Immune and neurotrophic (brain-derived neurotrophic factor—BDNF) alterations were determined in the prefrontal cortex (PFC), hippocampus (HC), and hypothalamus (HT). Since the incidence and clinical manifestations of neurodevelopmental disorders present significant sex-related differences, we sought to distinctly evaluate male and female mice. While on PN35, LPS-challenged male mice presented depressive, anxiety-like, repetitive behavior, and working memory deficits; on PN70, only depressive- and anxiety-like behaviors were observed. Conversely, females presented

Temperament can be considered the basis of humor, behavior and personality, they have strong biological basis, early development of the individual. Evidences suggests that temperament and personality traits predispose to the mood disorders. Because of this, it is important to identify biological factors associated with various temperament characteristics, such as differences in gene expression and neurochemical markers to help further evidence related to the etiopathogenesis of mental disorders such as depression and BD. (HE) and low exploratory activity (LE) exposes or not paradoxical sleep deprivation in adolescence. In the evaluation of the neurobiological basis of temperament, HE and LE tests were selected according to their exploratory profile in an open field test, a model of mania induced by temperamental sleep deprivation was used. Behavioral tests for locomotor activity and exploratory analysis, anxiety, cognition, depression, gene expression investigation of the clock genes, oxidative stress and inflammation were evaluated. The results of this study show that as individual behavioral factors, the exploratory patterns can be characterized in rats. By doing a translation for the human being these exploratory patterns reflect temperamental characteristics that influence a variety of behaviors and neurochemical and genetic parameters in response to the environment. Thus, our results for a strong interaction between exploratory patterns in animals and stressful events in adolescence contributing to the development of behavioral control type depression or mania in adulthood, showing that a selection of animals based on their exploratory pattern may be an alternative Interesting for conducting research with models with translational validity in psychiatry. O temperamento pode ser considerado como a base do humor, do comportamento e da personalidade, tem uma base biológica forte, manifesta-se cedo no desenvolvimento do indivíduo, norteia a formação dos hábitos sendo relativamente estável no decorrer do tempo. Evidências sugerem que o temperamento e os traços de personalidade predispõem aos transtornos de humor. Em função disso, é importante identificar fatores biológicos associados às distintas características do temperamento, como diferenças na expressão gênica e marcadores neuroquímicos para ajudar a dar mais evidências relacionadas à etiopatogenia de transtornos mentais como depressão e TAB. Dessa forma, o presente estudo tem como objetivo determinar alterações geno-fenotípicas em ratos adultos com elevada (HE) e baixa atividade exploratória (LE) expostos ou não à privação de sono paradoxal na adolescência. Na avaliação das bases neurobiológicas do temperamento foram selecionados ratos HE e LE de acordo com o seu perfil exploratório em um teste campo aberto, dessa forma foi utilizado um modelo de mania induzido por privação do sono de base temperamental. Foram avaliados testes comportamentais para atividade locomotora e exploratória, ansiedade, cognição, depressão, investigação de expressão gênica dos genes do relógio, estresse oxidativo e inflamação. Os resultados deste estudo mostraram que as diferenças comportamentais individuais, aqui chamadas padrões exploratórios podem ser caracterizadas em ratos. Fazendo uma translação para o ser humano estes padrões exploratórios refletem características temperamentais que influenciam uma variedade de comportamentos e parâmetros neuroquímicos e genéticos em resposta ao meio ambiente. Dessa forma, nossos resultados apontam para uma forte interação entre padrões exploratórios em animais (associados ao temperamento no ser humano) e eventos estressores na adolescência contribuindo para o desenvolvimento de alterações comportamentais tipo depressão ou mania na idade adulta, mostrando que a seleção de animais com base no seu padrão exploratório pode ser uma alternativa interessante para a condução de pesquisas com modelos animais com validade translacional em psiquiatria.

This study aimed to investigate the in vitro antioxidant activity of the novel anticonvulsant levetiracetam and benzodiazepine clonazepam. To do this, the mice brain homogenates were incubated with levetiracetam (50, 100 or 200 g/ml) or clonazepam (50, 100 or 200 g/ml), and then, submitted to heating at 37°C for 1 h. Ascorbic acid (vitamin C, 200 g/ml) was used as reference antioxidant drug. The markers of oxidative stress, such as lipid peroxidation, nitrite-nitrate content, catalase activity, and reduced glutathione (GSH) levels, were measured in brain homogenates. The group submitted to the heating-induced oxidative stress showed an increase in lipid peroxidation, nitrite-nitrate content, and catalase activity. Previous incubation with levetiracetam and clonazepam, mainly at lower doses (50 and 100 g/ml), and similarly to vitamin C, prevented these pro-oxidative changes, reducing the lipid peroxidation, nitrite-nitrate contents and catalase activity, and increasing GSH levels. These findings demonstrate antioxidant properties of levetiracetam and clonazepam, and help to elucidate the role of protection against oxidative stress in the neuroprotective mechanism of antiepileptic drugs.

Arthropod venoms are potential sources of neuroactive substances, providing new tools for the design of drugs. The aim of this study was to evaluate the effects of Dinoponera quadriceps venom (DqV) on seizure models in mice induced by pentylenetetrazole (PTZ), pilocarpine, and strychnine. In the PTZ model, intraperitoneal treatment with DqV (0.5 mg/kg) increased the time until the first seizure and the percentage of survival (155.4 ± 27.7 s/12.5%, p < 0.05) compared to the control group (79.75 ± 3.97 s/0%), whereas endovenous treatment (0.1 and 0.5 mg/kg) decreased the time until the first seizure (0.1 mg/kg: 77.83 ± 5.3 s versus 101.0 ± 3.3 s in the control group; 0.5 mg/kg: 74.43 ± 3.9 s versus 101.0 ± 3.3 s for the control group, p < 0.05). We did not observe significant changes in the pilocarpine- and strychnine-induced seizure models. In assays that measured oxidative parameters in the PTZ model, intraperitoneal treatment with DqV (0.5 and 2.0 mg/kg) only decreased the levels of MDA and nitrite in the cortex. However, endovenous treatment with DqV (0.1 and 0.5 mg/kg) increased the levels of MDA in the cortex and hippocampus and at a dose of 0.5 mg/kg in the striatum. Moreover, increased in nitrite content was observed in all three of the brain regions analyzed. Taken together, the D. quadriceps venom caused both neuroprotective and neurotoxic effects in a PTZ-induced seizure model, and this effect was dependent on the route of administration used.

The study aimed at evaluating the effects of the educational video use to promote the attachment between HIV positive mother and her son after six months of contact between them.This is an exploratory-descriptive study with a qualitative approach. Data was collected through semi-structured interviews. The sampling was intentional. The plan of analysis consisted of the following steps: the constitution of the corpus, definition of unit analysis, data categorization and analysis through categories. This study showed that, despite the difficulties and obstacles imposed by HIV / AIDS, by the treatment and the doubts present in daily life, HIV mothers develop strategies that enable them to live and better deal with the disease, without forgetting their role as a mother.

Epilepsy is the most common neurological disorder, affecting 50 million people worldwide, 40 million of them in developed countries. People of all races, genders, socioeconomic conditions and regions are affected. The pilocarpine (P400) is a cholinergic agonist characterized by inducing seizures evolving to status epilepticus, similar to human temporal lobe epilepsy. The pentylenetetrazole (PTZ) is a GABA antagonist that mimics the small-mal seizures (absence seizure) and tonic-clonic seizures in humans. The strychnine is a potent convulsant and acts mainly as a selective antagonist of postsynaptic inhibition mediated by glycine. Its main action is to increase the excitability of the spinal reflex . The convulsant picrotoxin is an agent that blocks chloride channels activated by gamma-aminobutyric acid. Convulsant agents were administered intraperitoneally, 10 minutes after intravenous administration of carbapenêmcios With the development of this work, we found that pretreatment with imipenem or meropenem interfere with various neurotransmitter systems when animals are subjected to seizures induced by pilocarpine at a dose of 400mg/kg, 55mg/Kg at a dose of pentylenetetrazole, strychnine and picrotoxin 10mg/Kg 2mg/kg. This has been evidenced by increasing levels of excitatory amino acids such as glutamate and on the other hand, a decrease in levels of inhibitory amino acids such as GABA reinforcing the existence of a possible modulatory pathway of these amino acids in control and development of seizure occurs when pre-treatment with imipenem or meropenem Epilepsia é o mais freqüente distúrbio neurológico, atingindo 50 milhões de pessoas no mundo, 40 milhões delas em países desenvolvidos. Pessoas de todas as raças, sexos, condições socioeconômicas e regiões são acometidas. A pilocarpina (P400) é um agonista colinérgico que se caracteriza por induzir convulsões que evoluem para status epilépticus, similar à epilepsia do lobo temporal humana. O pentilenotetrazol (PTZ) é um antagonista GABA que mimetiza convulsões do pequeno-mal (crise de ausência) e do tipo tônico-clônico em humanos. A estricnina é um potente convulsivante e atua, principalmente, como antagonista competitivo seletivo da inibição pós-sináptica mediada pela glicina. Sua principal ação é o aumento da excitabilidade reflexa da medula. A picrotoxina é um agente convulsivante que bloqueia os canais de cloro ativados pelo ácido gama-aminobutírico. Os agentes convulsivantes foram administrados intraperitonialmente, após 10 minutos da administração intravenosa dos carbapenêmcios Com o desenvolvimento deste trabalho, podemos observar que o pré-tratamento com imipenem ou meropenem interfere com vários sistemas de neurotransmissores quando os animais são submetidos à convulsão induzida pela pilocarpina na dose de 400mg/kg, pentilenotetrazol na dose de 55mg/Kg, estricnina 2mg/Kg e picrotoxina 10mg/Kg. Tal efeito foi evidenciado através do aumento nos níveis de aminoácidos excitatórios como o glutamato e, por outro lado, uma diminuição nos níveis de aminoácidos inibitórios como o GABA reforçando a existência de uma possível via modulatória desses aminoácidos no controle e desenvolvimento de crises epilépticas quando ocorre o pré-tratamento com imipenem/cilastatina ou meropenem.