Efeitos do tratamento com antibióticos não absorvíveis na plasticidade sináptica de ratos Wistar

Os microrganismos que habitam o intestino constituem uma complexa comunidade que interage com o hospedeiro e influenciam seu estado fisiológico e patológico através de suas atividades metabólicas. Já se observou que estes também influenciam o funcionamento do encéfalo e o comportamento através de mecanismos não totalmente elucidados. Neste sentido, as alterações na composição destas populações bacterianas no intestino, induzidas por antibióticos, probióticos, prebióticos ou transplante fecal de microbiota, ajudam a ilustrar as influências dessas comunidades. Por exemplo, elas já foram relacionadas com diversas desordens como Transtorno do Espectro Autista, Alzheimer, doença do intestino irritável, obesidade, depressão. Entender como a microbiota influencia o cérebro e seus impactos é de enorme importância para ajudar encontrar novas terapias direcionadas a estas doenças. O presente estudo tem como objetivo observar os impactos a nível proteico de marcadores envolvidos em sinapses (Sinaptofisina) excitatórias (PSD95) e inibitórias (gefirina), e nos níveis de neurotransmissores GABA e glutamato nas regiões do córtex pré-frontal, parietal e hipocampo de ratos Wistar machos adultos, após tratamento de 7 dias com antibióticos (ATBs) não absorvíveis (neomicina e vancomicina). Nossos dados indicam que a atuação dos ATBs sobre o microbioma foi capaz de provocar alterações nos níveis de marcadores de sinaptofisina e PSD95 no córtex parietal e pré-frontal. Além disso, o tratamento resultou em alterações nos níveis basais e pós estimulação de glutamato no córtex pré-frontal, enquanto no córtex parietal houve alteração na liberação de GABA em relação ao basal. Não se observou alterações significativas no hipocampo. Em resumo, nossos dados agregam evidências de que agentes capazes de induzir alterações na microbiota intestinal podem potencialmente afetar a neuroquímica e plasticidade neuronal.The microorganisms that inhabit the intestine constitute a complex community that interacts with the host and influences its physiological and pathological state through its metabolic activities. It has already been observed that they still influence the functioning of the brain and behavior through mechanisms that have not been fully elucidated. Changes in the composition of these bacteria in the intestine, induced by antibiotics, probiotics, prebiotics or fecal microbiota transplant help to illustrate the influences of these communities and have been linked to several disorders such as Autistic Spectrum Disorder, Alzheimer, irritable bowel disease, obesity, depression . Understanding what influences the microbiota and its impacts is extremely important to help find new therapies targeting these diseases. The present study aims to observe the protein impacts of markers involved in synapses (Synaptophysin), excitatory (PSD95), inhibitory (Gefirina), and in the neurotransmitters GABA and glutamate in the regions of the prefrontal and parietal cortex and in the hippocampus of adult male Wistar rats after 7 days of treatment with non-absorbable antibiotics (ATBs) (neomycin and vancomycin). Our data indicate that the use of ATBs was able to cause changes in the levels of synapses and excitatory synapses (Synaptophysin and PSD95), in the parietal and prefrontal cortex. In addition to changes in baseline levels and after stimulation of high potassium medium, Glutamate in the prefrontal cortex, while in the parietal cortex there was a change in the percentage of GABA release compared to baseline. There were no significant changes in the hippocampus. In summary, our data add evidence that agents capable of inducing changes in the intestinal microbiota can potentially affect neurochemistry and neuronal plasticity

Neurobehavioral And Oxidative Stress Alterations Following Methylmercury And Retinyl Palmitate Co-Administration In Pregnant And Lactating Rats And Their Offspring

Fish consumption and ubiquitous methylmercury (MeHg) exposure represent a public health problem globally. Micronutrients presented in fish affects MeHg uptake/distribution. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. The present study aimed to examine the effects of both MeHg and retinyl palmitate administered to pregnant and lactating rats. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/Kg/day) and retinyl palmitate (7500 μg RAE1/Kg/day), either individually or in combination from the gestational day 0 to weaning. In dams, maternal behavior was scored. In neonatal and infant offspring, associative learning and neurodevelopment were evaluated. Further periadolescent male and female pups were assessed for open field, habituation and object recognition using episodic-like memory paradigm. Maternal and offspring redox parameters were evaluated. Our results showed no effects of MeHg-VitA co-administration in the quality of maternal care but showed subtle alterations in the pro-oxidant response of the hippocampus. In offspring, MeHg-VitA co-exposure affected early associative learning in neonatal pups, with no further modifications in neurodevelopment, and no locomotor or exploratory alterations in later developmental stages. Habituation was altered in a sex-dependent manner, but no overall memory disturbances were encountered

Effects Of Methylmercury And Retinol Palmitate Co-Administration In Rats During Pregnancy And Breastfeeding: Metabolic And Redox Parameters In Dams And Their Offspring

Ubiquitous low-dose methylmercury (MeHg) exposure through an increased fish consumption represents a global public health problem, especially among pregnant women. A plethora of micronutrients presented in fish affects MeHg uptake/distribution, but limited data is available. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. Therefore, the present study aimed to examine the effects of both MeHg and retinyl palmitate administered on pregnant and lactating rats in metabolic and redox parameters from dams and their offspring. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/kg/day) and retinyl palmitate (7500 µg RAE/kg/day) via gavage, either individually or in combination from the gestational day 0 to weaning. For dams (150 days old) and their offspring (31 days old), glycogen accumulation (hepatic and cardiac) and retinoid contents (plasma and liver) were analyzed. Hg deposition in liver tissue was quantified. Redox parameters (liver, kidney, and heart) were evaluated for both animals. Cytogenetic damage was analyzed with micronucleus test. Our results showed no general toxic or metabolic alterations in dams and their offspring by MeHg-VitA co-administration during pregnancy and lactation. However, increased lipoperoxidation in maternal liver and a disrupted pro-oxidant response in the heart of male pups was encountered, with apparently no particular effects in the antioxidant response in female offspring. GST activity in dam kidney was altered leading to possible redox disruption of this tissue with no alterations in offspring. Finally, the genomic damage was exacerbated in both male and female pups. In conclusion, low-dose MeHg exposure and retinyl palmitate supplementation during gestation and lactation produced a potentiated pro-oxidant effect, which was tissue-specific. Although this is a pre-clinical approach, we recommend precaution for pregnant women regarding food consumption, and we encourage more epidemiological studies to assess possible modulations effects of MeHg-VitA co-administration at safe or inadvertently used doses in humans, which may be related to specific pathologies in mothers and their children

Efectos de la coadministración de metilmercurio y palmitato de retinol en ratas durante el embarazo y la lactancia materna: parámetros metabólicos y redox en las madres y sus crías

Ubiquitous low-dose methylmercury (MeHg) exposure through an increased fish consumption represents a global public health problem, especially among pregnant women. A plethora of micronutrients presented in fish affects MeHg uptake/distribution, but limited data is available. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. Therefore, the present study aimed to examine the effects of both MeHg and retinyl palmitate administered on pregnant and lactating rats in metabolic and redox parameters from dams and their offspring. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/kg/day) and retinyl palmitate (7500 µg RAE/kg/day) via gavage, either individually or in combination from the gestational day 0 to weaning. For dams (150 days old) and their offspring (31 days old), glycogen accumulation (hepatic and cardiac) and retinoid contents (plasma and liver) were analyzed. Hg deposition in liver tissue was quantified. Redox parameters (liver, kidney, and heart) were evaluated for both animals. Cytogenetic damage was analyzed with micronucleus test. Our results showed no general toxic or metabolic alterations in dams and their offspring by MeHg-VitA coadministration during pregnancy and lactation. However, increased lipoperoxidation in maternal liver and a disrupted pro-oxidant response in the heart of male pups was encountered, with apparently no particular effects in the antioxidant response in female offspring. GST activity in dam kidney was altered leading to possible redox disruption of this tissue with no alterations in offspring. Finally, the genomic damage was exacerbated in both male and female pups. In conclusion, low-dose MeHg exposure and retinyl palmitate supplementation during gestation and lactation produced a potentiated pro-oxidant effect, which was tissue-specific. Although this is a pre-clinical approach, we recommend precaution for pregnant women regarding food consumption, and we encourage more epidemiological studies to assess possible modulations effects of MeHg-VitA co- administration at safe or inadvertently used doses in humans, which may be related to specific pathologies in mothers and their children.Exposición ubicua a baja dosis de metilmercurio (mehg) a través de un aumento de los peces el consumo representa un problema de salud pública mundial, especialmente entre las embarazadas mujeres. Una gran cantidad de micronutrientes presentados en pescado afecta mehg captación / distribución, pero se dispone de datos limitados. Vitamina a (vita), otro pescado. El micronutriente se usa en suplementos nutricionales, especialmente durante el embarazo. Sin embargo, no hay información sobre los efectos en la salud que surgen de su exposición combinada. Por lo tanto, el presente estudio tuvo como objetivo examinar los efectos de mehg y palmitato de retinilo administrados en ratas gestantes y lactantes en parámetros metabólicos y redox de las represas y su descendencia. Treinta wistar ratas hembra fueron suplementadas oralmente con mehg (0,5 mg / kg / día) y retinilo palmitato (7500 µg rae / kg / día) por sonda, individualmente o en combinación desde el día gestacional 0 hasta el destete. Para las presas (150 días de antigüedad) y sus crías. (31 días de edad), acumulación de glucógeno (hepático y cardíaco) y retinoides. (plasma e hígado) fueron analizados. Se cuantificó la deposición de hg en tejido hepático. Se evaluaron los parámetros redox (hígado, riñón y corazón) para ambos animales. El daño citogenético se analizó con prueba de micronúcleo. Nuestros resultados no mostraron alteraciones generales tóxicas o metabólicas en las madres y su descendencia por coadministración de mehg-vita durante el embarazo y la lactancia. Sin embargo, aumentó lipoperoxidación en el hígado materno y una respuesta prooxidante interrumpida en el corazón. De cachorros machos, aparentemente sin efectos particulares en la respuesta antioxidante en la descendencia femenina. Se alteró la actividad de gst en riñón de la presa. Llevando a una posible alteración redox de este tejido sin alteraciones en la descendencia. Finalmente, el daño genómico se exacerbó tanto en cachorros machos como hembras. En conclusión, la exposición a baja dosis de mehg y la suplementación con palmitato de retinilo durante la gestación y la lactancia produjeron un efecto prooxidante potenciado, que fue tejido específico, aunque este es un enfoque preclínico, recomendamos precaución. Para las mujeres embarazadas en relación con el consumo de alimentos, y animamos estudios epidemiológicos para evaluar los posibles efectos moduladores de la co-mehg-vita la administración a dosis seguras o inadvertidamente utilizadas en humanos, que pueden ser relacionados con patologías específicas en madres y sus hijo