Perinatal exposure to an aromatase inhibitor glyphosate-base herbicide reduced male and female social behavior in juvenile age and the sexual behavior at adult female rats / Exposição perinatal ao inibidor da aromatase a base de glifosato reduz o comportamento social de machos e fêmeas e o comportamento sexual de ratas

Objectives: The herbicide glyphosate, a pesticide used in agriculture to control weeds, both in food crops and in other agricultural areas, has been identified as an endocrine modulator through the inhibition of aromatase activity and the activation of estrogen receptors. The present study examined the effects of a glyphosate-based herbicide (Roundup® (GLY-BH) on sexual dimorphism of rats after perinatal exposure to low and high GLY-BH in males and females offspring. Methods: Two groups of pregnant rats were treated with two doses of GLY-BH (50 or 150 mg/kg) from day 15 of gestation (GD15) to postnatal day 7 (PND7). Play fighting behavior was observed at the juvenile stage and during social and sexual behaviors in adulthood. Results: Perinatal GLY-BH exposure reduced male and female body weight at 28, 75, and 90 days of age. The play fighting behavior was decreased in both sexes, but female rats were more affected. The sexual behaviors were reduced only in females. Conclusions: Perinatal exposure to both doses of GLY-BH promoted sexually dimorphic effects in both juvenile and adulthood stages. These effects were attributed to the inhibition of aromatase activity induced by exposure to GLY-BH in the perinatal period.(AU)

Objetivos: O glifosato é um herbicida não seletivo, usado em muitas culturas alimentares e não alimentares e em áreas não agrícolas, sendo que os produtos a base de glifosato atuam como moduladores das funções endócrinas por meio da inibição da atividade da aromatase e da ativação de receptores de estrógeno. O presente estudo avaliou os efeitos do herbicida Roundup® (GLY-BH) à base de glifosato, em comportamentos sexualmente dimórficos de ratos após exposição perinatal a doses baixas e altas de GLY-BH no período perinatal. Métodos: Ratas prenhas foram tratadas com 50 ou 150 mg/kg de GLY-BH do 15º dia de gestação (GD15) ao 7º dia de lactação (LD7). O comportamento de luta/brincar foi observado na fase juvenil e os comportamentos social e sexual na idade adulta. Resultados: a exposição perinatal a GLY-BH reduziu o peso corporal de machos e fêmeas aos 28, 75 e 90 dias de idade. O comportamento de luta/brincar diminuiu em ambos os sexos, sendo as ratas foram as mais afetadas. O comportamento sexual foi reduzido apenas nas fêmeas. Conclusões: A exposição perinatal a ambas as doses do GLY- BH promoveu tanto na idade juvenil como na idade adulta, efeitos sexualmente dimórficos. Esses efeitos foram atribuídos à inibição da atividade da aromatase induzida exposição perinatal ao GLY-BH.(AU)

Increased Endocannabinoid Signaling Reduces Social Motivation in Intact Rats and Does Not Affect Animals Submitted to Early-Life Seizures.

The early life status epilepticus (SE) causes high anxiety and chronic socialization abnormalities, revealed by a low preference for social novelty and deficit in social discrimination. This study investigated the involvement of the endocannabinoid system on the sociability in this model, due to its role in social motivation regulation. Male Wistar rats at postnatal day 9 were subjected to pilocarpine-induced neonatal SE and controls received saline. From P60 the groups received vehicle or JZL195 2 h before each behavioral test to increase endocannabinoids availability. In the sociability test, animals subjected to neonatal SE exhibited impaired sociability, characterized by social discrimination deficit, which was unaffected by the JZL195 treatment. In contrast, JZL195-treated control rats showed low sociability and impaired social discrimination. The negative impact of JZL195 over the sociability in control rats and the lack of effect in animals subjected to neonatal SE was confirmed in the social memory paradigm. In this paradigm, as expected for vehicle-treated control rats, the investigation toward the same social stimulus decreased with the sequential exposition and increased toward a novel stimulus. In animals subjected to neonatal SE, regardless of the treatment, as well as in JZL195-treated control rats, the investigation toward the same social stimulus was significantly reduced with no improvement toward a novel stimulus. Concerning the locomotion, the JZL195 increased it only in control rats. After behavioral tests, brain tissues of untreated animals were used for CB1 receptor quantification by Elisa and for gene expression by RT-PCR: no difference between control and experimental animals was noticed. The results reinforce the evidence that the early SE causes chronic socialization abnormalities, revealed by the low social interest for novelty and impaired social discrimination. The dual FAAH/MAGL inhibitor (JZL195) administration before the social encounter impaired the social interaction in intact rats with no effect in animals subjected to early-life seizures.

Green tea improves the metabolism of peripheral tissues in ß3-adrenergic receptor-knockout mice.

Our goal was to establish the requirement of ß3 adrenoceptor (ß3Adr) for green tea (GT) effects on the energy metabolism of obese mice. This study was carried out in wild-type (WT) and ß3Adr knockout (KO) male mice fed with a standard diet or a high-fat diet (HFD/16 weeks) treated or not with GT (0.5 g/kg of body weight (BW)/12 weeks). GT-treatment attenuated final BW, BW gain, and adiposity index increased by HFD, improving insulin resistance (IR) and FGF21 level, without changing the food intake of WT mice. GT-treatment of ß3AdrKO mice attenuated only IR, denoting GT-effects independent of ß3Adr. We observed increased lipolysis accompanied by decreased adipocyte size in white adipose tissue (WAT) as well as browning of the subcutaneous WAT induced by GT in a way dependent on ß3Adr. In brown adipose tissue (BAT) mRNA levels of lipolytic/oxidative genes, including ß3Adr/Ucp1 and energy expenditure (EE) was increased by GT dependent on ß3Adr. GT-treatment increased adiponectin independent of ß3Adr. Also, independent of ß3Adr pathway GT promoted an increase in ß2Adr/Ucp1 mRNA levels and EE in BAT whereas; in the liver, GT has a dual role in increasing lipid synthesis and oxidation. These data lead us to suggest that GT uses ß3Adr pathway activation to achieve some of its beneficial health effects.

Dataset on sociability, cognitive function, gene and protein expression of molecules involved in social behavior, reward system and synapse function following early-life status epilepticus in Wistar rats.

Early-life status epilepticus produces deficit in social interaction and vocalization, enhances anxiety, no cognitive impairment and alters functional connectivity within the hippocampus (CA3-CA1) and between the hippocampus and prefrontal cortex [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], but the underlying mechanisms remain unknown. This data article contains behavioral and molecular data of the adult male Wistar rats subjected to early life pilocarpine-induced seizures. Animal's behaviors were assessed to social memory and social motivation, working and reference memories and cognitive flexibility. The brain tissues (hypothalamus, hippocampus, amygdala, and striatum) were probed to gene and protein expression of molecules related to social behavior, reward system and synaptic function.

Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition.

Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95.

Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition

ABSTRACT Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95

Muscle IGF-1-induced skeletal muscle hypertrophy evokes higher insulin sensitivity and carbohydrate use as preferential energy substrate.

We characterized the metabolic profile of transgenic mice exhibiting enhanced muscle mass driven by increased mIGF-1 expression (MLC/mIGF-1). As expected, 6-month-old MLC/mIGF-1 mice were heavier than age-matched wild type (WT) mice (37.4 ± 0.3 versus 31.8 ± 0.6 g, resp.). MLC/mIGF-1 mice had higher respiratory quotient when compared to WT (0.9 ± 0.03 versus 0.74 ± 0.02, resp.) suggesting a preference for carbohydrate as the major fuel source. MLC/mIGF-1 mice had a higher rate of glucose disposal when compared to WT (3.25 ± 0.14 versus 2.39 ± 0.03%/min, resp.). The higher disposal rate correlated to ∼ 2-fold higher GLUT4 content in the extensor digitorum longus (EDL) muscle. Analysis of mRNA content for the glycolysis-related gene PFK-1 showed ∼ 3-fold upregulation in MLC/mIGF-1 animals. We also found a 50% downregulation of PGC1α mRNA levels in MLC/mIGF-1 mouse EDL muscle, suggesting less abundant mitochondria in this tissue. We found no difference in the expression of PPARα and PPARß/δ, suggesting no modulation of key elements in oxidative metabolism. These data together suggest a shift in metabolism towards higher carbohydrate utilization, and that could explain the increased insulin sensitivity of hypertrophied skeletal muscle in MLC/mIGF-1 mice.