Relationship between maternal biological features, environmental factors, and newborn neuromotor development associated with visual fixation abilities.

Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.

Coping with the experience of frustration throughout life: Sex- and age-specific effects of early life stress on the susceptibility to reward devaluation.

Early life stress may lead to lifelong impairments in psychophysiological functions, including emotional and reward systems. Unpredicted decrease in reward magnitude generates a negative emotional state (frustration) that may be involved with susceptibility to psychiatric disorders. We evaluated, in adolescents and adult rats of both sexes, whether maternal separation (MS) alters the ability to cope with an unexpected reduction of reward later in life. Litters of Wistar rats were divided into controls (non handled - NH) or subjected to MS. Animals were trained to find sugary cereal pellets; later the amount was reduced. Increased latency to reach the reward-associated area indicates higher inability to regulate frustration. The dorsal hippocampus (dHC) and basolateral amygdala (BLA) were evaluated for protein levels of NMDA receptor subunits (GluN2A/GluN2B), synaptophysin, PSD95, SNAP-25 and CRF1. We found that adult MS males had greater vulnerability to reward reduction, together with decreased GluN2A and increased GluN2B immunocontent in the dHC. MS females and adolescents did not differ from controls. We concluded that MS enhances the response to frustration in adult males. The change in the ratio of GluN2A and GluN2B subunits in dHC could be related to a stronger, more difficult to update memory of the aversive experience.

Acrobatic training prevents learning impairments and astrocyte remodeling in the hippocampus of rats undergoing chronic cerebral hypoperfusion: sex-specific benefits.

Background: Chronic cerebral hypoperfusion (CCH) leads to memory and learning impairments associated with degeneration and gliosis in the hippocampus. Treatment with physical exercise carries different therapeutic benefits for each sex. We investigated the effects of acrobatic training on astrocyte remodeling in the CA1 and CA3 subfields of the hippocampus and spatial memory impairment in male and female rats at different stages of the two-vessel occlusion (2VO) model. Methods: Wistar rats were randomly allocated into four groups of males and females: 2VO acrobatic, 2VO sedentary, sham acrobatic, and sham sedentary. The acrobatic training was performed for 4 weeks prior to the 2VO procedure. Brain samples were collected for morphological and biochemical analysis at 3 and 7 days after 2VO. The dorsal hippocampi were removed and prepared for Western blot quantification of Akt, p-Akt, COX IV, cleaved caspase-3, PARP, and GFAP. GFAP immunofluorescence was performed on slices of the hippocampus to count astrocytes and apply the Sholl's circle technique. The Morris water maze was run after 45 days of 2VO. Results: Acutely, the trained female rats showed increased PARP expression, and the 2VO-trained rats of both sexes presented increased GFAP levels in Western blot. Training, mainly in males, induced an increase in the number of astrocytes in the CA1 subfield. The 2VO rats presented branched astrocytes, while acrobatic training prevented branching. However, the 2VO-induced spatial memory impairment was partially prevented by the acrobatic training. Conclusion: Acrobatic training restricted the astrocytic remodeling caused by 2VO in the CA1 and CA3 subfields of the hippocampus. The improvement in spatial memory was associated with more organized glial scarring in the trained rats and better cell viability observed in females.

Neuroinflammation, blood-brain barrier dysfunction, hippocampal atrophy and delayed neurodevelopment: Contributions for a rat model of congenital Zika syndrome.

The congenital Zika syndrome (CZS) has been characterized as a set of several brain changes, such as reduced brain volume and subcortical calcifications, in addition to cognitive deficits. Microcephaly is one of the possible complications found in newborns exposed to Zika virus (ZIKV) during pregnancy, although it is an impacting clinical sign. This study aimed to investigate the consequences of a model of congenital ZIKV infection by evaluating the histopathology, blood-brain barrier, and neuroinflammation in pup rats 24 h after birth, and neurodevelopment of the offspring. Pregnant rats were inoculated subcutaneously with ZIKV-BR at the dose 1 × 107 plaque-forming unit (PFU mL-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). A set of pups, 24 h after birth, was euthanized. The brain was collected and later evaluated for the histopathology of brain structures through histological analysis. Additionally, analyses of the blood-brain barrier were conducted using western blotting, and neuroinflammation was assessed using ELISA. Another set of animals was evaluated on postnatal days 3, 6, 9, and 12 for neurodevelopment by observing the developmental milestones. Our results revealed hippocampal atrophy in ZIKV animals, in addition to changes in the blood-brain barrier structure and pro-inflammatory cytokines expression increase. Regarding neurodevelopment, a delay in important reflexes during the neonatal period in ZIKV animals was observed. These findings advance the understanding of the pathophysiology of CZS and contribute to enhancing the rat model of CZS.

Produção de óxido nítrico no hipocampo: investigação do envolvimento do óxido nítrico sintase neuronal no desenvolvimento de comportamentos ansiosos em animais submetidos a estresse neonatal / Hippocampal nitric oxide production: investigation of the role of neuronal nitric oxide synthase in the development of anxiety-like behaviors in animals subjected to neonatal stress

Introdução: Estudos indicam que o trauma precoce e o sistema serotoninérgico estão relacionados ao desenvolvimento de ansiedade. Esta relação poderia ser mediada pela enzima óxido nítrico sintase neuronal (nNOS), que tem papel importante no funcionamento dos receptores de serotonina. Objetivo: Investigar, através da mensuração do óxido nítrico (NO) no hipocampo, o possível envolvimento da nNOS no desenvolvimento de ansiedade em um modelo animal de adversidade no início da vida, baseado na qualidade do cuidado materno. Métodos: Ao segundo dia de vida, genitoras Wistar e suas ninhadas foram divididas em dois grupos: intervenção, com redução do material para a confecção do ninho, ou controle. O comportamento materno foi observado do dia 1 ao dia 9 de vida. Na vida adulta, realizaram-se testes comportamentais e determinaram-se os níveis hipocampais de NO, através da mensuração de seus produtos de degradação. Resultados: Observou-se um maior comportamento do tipo ansioso no grupo intervenção, cujas genitoras apresentaram maior contato de baixa qualidade com seus filhotes. Nos machos, o cuidado materno de baixa qualidade correlacionou-se negativamente com o tempo no braço aberto e a frequência de mergulhos (r=-0,4;p=0,03) avaliados no labirinto em cruz elevado. O comportamento materno de lamber os filhotes correlacionou-se com a frequência de mergulhos em ambos os sexos (r=0,5;p<0,001). A quantidade de NO no hipocampo não diferiu entre os grupos. Conclusão: Uma maior atividade da nNOS não parece estar envolvida no comportamento ansioso observado neste modelo animal, no entanto a relação mãe-filhote, alterada por um ambiente neonatal adverso, teve impacto sobre o comportamento ansioso de forma sexo específica.

Background: Studies have shown that an adverse early life environment and the serotonergic system are related to the development of anxiety. This association could be mediated by neuronal nitric oxide synthase (nNOS), an enzyme that plays an important role in serotonin receptor functioning. Aim: To investigate the possible role of nNOS in the development of anxiety by measuring hippocampal nitric oxide (NO) in an animal model of neonatal stress, based on the quality of maternal care. Methods: On the second day of life, Wistar dams and their litters where divided in two groups: intervention, with limited access to nesting material, or control. Maternal behavior was observed from day 1 to 9 of life. In adult life, behavioral tests were performed and hippocampal NO levels were determined by measuring its degradation products. Results: There was more frequent anxiety-like behavior in the intervention group, whose dams showed low quality contact with their pups more often. In males, low quality maternal care was negatively correlated with time spent in open arms and frequency of head dips (r=-0.4; p=0.03) assessed using an elevated plus maze. Licking and grooming score was correlated with frequency of head dips in both sexes (r=0.5;p<0.001). Hippocampal NO levels were not different between groups (p=0.992). Conclusion: A higher nNOS activity does not seem to be involved in anxiety-like behavior observed in this animal model, however the relationship between dam and pup, modified by an adverse early life environment, had a different impact on anxiety behavior between sexes.

Lithium and methylphenidate: opposite effects on perirenal brown fat / Lítio e metilfenidato: efeitos opostos sobre a gordura perirrenal

OBJECTIVE: To evaluate the effects of the administration of lithium to adult rats on brown (perirenal) and white (inguinal) adipose tissues and to assess whether methylphenidate modulates lithium effects. METHODS: Twenty-five adult male Wistar rats were fed with either regular or lithium-containing chow for 30 days. Between days 15 to 30 of treatment, animals received daily intraperitoneal administrations of either methylphenidate or saline. RESULTS: Lithium significantly reduced perirenal fat, and this effect was minimized by the administration of methylphenidate. There were no significant differences between the groups in terms of the effects of lithium on inguinal fat. CONCLUSION: Our findings suggest that different effects on white and brown tissue distribution may be involved in lithium-induced weight gain.

OBJETIVO: Avaliar como a administração de lítio afeta o tecido adiposo marrom (perirrenal) e branco (inguinal) e se o metilfenidato modula os efeitos do lítio. MÉTODOS: Vinte e cinco ratos Wistar adultos machos foram alimentados com ração normal ou contendo lítio por 30 dias. Entre os dias 15 e 30 de tratamento, os animais receberam doses intraperitoneais diárias de metilfenidato ou solução salina. RESULTADOS: A administração de lítio reduziu significativamente a gordura perirrenal. Esse efeito foi reduzido com a administração de metilfenidato. Não houve diferenças significativas entre os grupos em relação à gordura inguinal. CONCLUSÃO: Os achados sugerem que efeitos diferenciados sobre os tecidos adiposos marrom e branco podem estar envolvidos no ganho de peso induzido pelo tratamento com lítio.