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      Comportamento materno: uma revisão da inter-relação com a toxicologia do desenvolvimento em roedores Translated title: Developmental toxicology: a review of maternal behavioral aspects in mammals Translated title: Comportamiento materno: una revisión de la inter-relación con la toxicología del desarrollo en roedores

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          Abstract

          A toxicologia do desenvolvimento é uma ciência que estuda os efeitos adversos que ocorrem nos organismos em desenvolvimento, expostos a diferentes agentes químicos antes da concepção, durante o desenvolvimento pré-natal e pós-natal até a puberdade. Recentemente, o interesse pelo estudo do comportamento materno no contexto da toxicologia do desenvolvimento cresceu, uma vez que, os cuidados com o neonato de mamíferos podem causar grande impacto no seu desenvolvimento. Desse modo, essa revisão teve como objetivo elucidar o comportamento materno e sua importância para o desenvolvimento da saúde mental e física da prole, bem como, as consequências deletérias da negligência materna e sua inter-relação com toxicologia do desenvolvimento, focando nos aspectos do comportamento materno em roedores, por esse ser o modelo de escolha em estudo de toxicidade pré-clínicos. Para tanto, foi realizado levantamento bibliográfico em livros, periódicos e teses obtidos nas bases de dados PubMed, Scopus e ScienceDirect entre os anos de 1966 e 2017. Os trabalhos selecionados mostraram que o comportamento materno é fundamental para o desenvolvimento da prole de roedores. Assim, alterações no vínculo mãe-filhote podem gerar distúrbios sociais permanentes nos filhotes, evidenciando a importância de estudos no âmbito comportamental. Esses estudos também mostraram a importância da regulação endócrina e neuroquímica na manifestação do comportamento materno, em especial o neurotransmissor dopamina, já que ao controlar a síntese e secreção de prolactina, atua na manifestação do vínculo mãe-filhote, necessário para despertar os cuidados da mãe no desenvolvimento da prole. Outro aspecto relevante foi que substâncias como praguicidas e fármacos, quando presentes no período gestacional, podem levar a modificações permanentes às gerações futuras, tanto de origem física-anatômica quanto relacionados ao comportamento.

          Translated abstract

          Developmental toxicology is a science that studies the adverse effects that occur in developing organisms, exposed to different chemical agents before conception, during prenatal and postnatal development until puberty. Recently, the study of maternal behavior in the context of developmental toxicology has gained interest, since the care of mammal's neonate can have a great impact on their development. Thus, this review aimed to elucidate maternal behavior and its importance for the development of the mental and physical health of offspring, as well as the deleterious consequences of maternal neglect and its interrelationship with developmental toxicology, focusing on aspects of maternal behavior toxicity in rodents, as they are the first choice in preclinical toxicity studies. For this purpose, a bibliographic survey was carried out in books, periodicals and theses obtained from the PubMed, Scopus and ScienceDirect databases between 1966 and 2017. Selected papers showed that maternal behavior is fundamental for the development of rodent offspring. Therefore, changes in the mother-infant bond may generate permanent social disturbances in the offspring, evidencing the importance of behavioral studies. These studies also showed the importance of endocrine and neurochemical regulation in the manifestation of maternal behavior, especially the neurotransmitter dopamine, since it controls the synthesis and secretion of prolactin, a hormone that acts in the manifestation of the mother-child bond necessary to awaken the mother's care in offspring development. Another relevant aspect is that substances such as pesticides and drugs, when present in the gestational period, can lead to permanent modifications to future generations.

          Translated abstract

          La toxicología del desarrollo es una ciencia que estudia los efectos adversos que ocurren en los organismos en desarrollo, expuestos a diferentes agentes químicos antes de la concepción, durante el desarrollo prenatal y postnatal hasta la pubertad. Recientemente, ha ganado interés el estudio del comportamiento materno en el contexto de la toxicología del desarrollo, ya que los cuidados con el neonato de mamíferos pueden causar gran impacto en su desarrollo. De este modo, esta revisión tuvo como objetivo elucidar el comportamiento materno y su importancia para el desarrollo de la salud mental y física de la prole, así como, las consecuencias deletéreas de la negligencia materna y su interrelación con la toxicología del desarrollo, enfocándose en los aspectos del comportamiento En el caso de los roedores, por ser el modelo de elección en estudio de toxicidad preclínica. Para ello, se realizó un levantamiento bibliográfico en libros, periódicos y tesis obtenidos en las bases de datos PubMed, Scopus y ScienceDirect entre los años de 1966 y 2017. Los trabajos seleccionados mostraron que el comportamiento materno es fundamental para el desarrollo de la prole de roedores. Así, alteraciones en el vínculo madre-cachorro pueden generar disturbios sociales permanentes en los cachorros, evidenciando la importancia de estudios en el ámbito comportamental. Estos estudios también mostraron la importancia de la regulación endocrina y neuroquímica en la manifestación del comportamiento materno, en especial el neurotransmisor dopamina, ya que al controlar la síntesis y secreción de prolactina, actúa en la manifestación del vínculo madre-hijo, necesario para despertar los cuidados de la madre En el desarrollo de la descendencia. Otro aspecto relevante fue que sustancias como plaguicidas y fármacos, como presentes en el período gestacional, pueden llevar a modificaciones permanentes a las generaciones futuras, tanto de origen físico-anatómico y relacionadas con el comportamiento.

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          Most cited references80

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          Several developments during the past 15 years have profoundly affected our understanding of the vomeronasal system (VNS) of vertebrates. In the mid 1990s, the vomeronasal epithelium of mammals was found to contain two populations of receptor cells, based on their expression of G-proteins. These two populations of neurons were subsequently found to project their axons to different parts of the accessory olfactory bulb (AOB), forming the basis of segregated pathways with possibly heterogeneous functions. A related discovery was the cloning of members of at least two gene families of putative vomeronasal G-protein-coupled receptors (GPRs) in the vomeronasal epithelium. Ligand binding to these receptors was found to activate a phospholipase C (PLC)-dependent signal transduction pathway that primarily involves an increase in intracellular inositol-tris-phosphate and intracellular calcium. In contrast to what was previously believed, neuron replacement in the vomeronasal epithelium appears to occur through a process of vertical migration in most mammals. New anatomical studies of the central pathways of the olfactory and vomeronasal systems indicated that these two systems converge on neurons in the telencephalon, providing an anatomical substrate for functional interactions. Combined anatomical, physiological and behavioral studies in mice provided new information that furthered our understanding of one of the most striking pheromonal phenomena, the Bruce effect. Finally, contrary to prior observations, new anatomical studies indicated that a vomeronasal organ (VNO) was present in human adults and reports were published indicating that this system might be functional. These latter observations are still controversial and require confirmation from independent laboratories.
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            Brain oxytocin correlates with maternal aggression: link to anxiety.

            The oxytocinergic system is critically involved in the regulation of maternal behavior, which includes maternal aggression. Because aggression has been linked to anxiety, we investigated the maternal aggression and the role of brain oxytocin in lactating Wistar rats selectively bred for high anxiety-related behavior (HAB) or low anxiety-related behavior (LAB) during the 10 min maternal defense test. HAB dams displayed more maternal aggression against a virgin intruder compared with LAB dams, resulting in more defensive behavior and higher anxiety of HAB-defeated virgins. The different levels of aggression were accompanied by opposite oxytocin release patterns within the paraventricular nucleus (PVN; HAB, increase; LAB, decrease). Furthermore, oxytocin release was higher within the central nucleus of the amygdala (CeA) of HAB dams compared with LABs. A direct correlation between the offensive behavior displayed during the maternal defense test and local oxytocin release was found in both the PVN and CeA. Using retrodialysis, blockade of endogenous oxytocin action by infusion of an oxytocin receptor antagonist (des-Gly-NH2,d(CH2)5[Tyr(Me)2,Thr4]OVT) into the PVN or CeA reduced maternal aggression of HAB dams, whereas infusion of synthetic oxytocin into the PVN tended to increase aggression toward the intruder in LAB dams. There were no significant differences in oxytocin receptor mRNA expression or oxytocin receptor binding between lactating HAB and LAB dams. Therefore, differences in intracerebral release patterns of oxytocin, rather than differences at the level of oxytocin receptors, are critical for the regulation of maternal aggressive behavior.
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              Growth retardation and altered autonomic control in mice lacking brain serotonin.

              Serotonin synthesis in mammals is initiated by 2 distinct tryptophan hydroxylases (TPH), TPH1 and TPH2. By genetically ablating TPH2, we created mice (Tph2(-/-)) that lack serotonin in the central nervous system. Surprisingly, these mice can be born and survive until adulthood. However, depletion of serotonin signaling in the brain leads to growth retardation and 50% lethality in the first 4 weeks of postnatal life. Telemetric monitoring revealed more extended daytime sleep, suppressed respiration, altered body temperature control, and decreased blood pressure (BP) and heart rate (HR) during nighttime in Tph2(-/-) mice. Moreover, Tph2(-/-) females, despite being fertile and producing milk, exhibit impaired maternal care leading to poor survival of their pups. These data confirm that the majority of central serotonin is generated by TPH2. TPH2-derived serotonin is involved in the regulation of behavior and autonomic pathways but is not essential for adult life.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                cpdd
                Cadernos de Pós-Graduação em Distúrbios do Desenvolvimento
                Cad. Pós-Grad. Distúrb. Desenvolv.
                Universidade Presbiteriana Mackenzie (São Paulo, SP, Brazil )
                1519-0307
                1809-4139
                June 2017
                : 17
                : 1
                : 08-25
                Affiliations
                [1] orgnameUniversidade Presbiteriana Mackenzie
                [4] orgnameUniversidade de São Paulo
                [3] orgnameUniversidade São Judas Tadeu
                [2] orgnameUniversidade de São Paulo
                Article
                S1519-03072017000100003
                10.5935/cadernosdisturbios.v17n1p8-25
                af5f6e68-f01b-4109-9f31-9c543786b7e3

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 03 August 2017
                : 16 March 2017
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 82, Pages: 18
                Product

                SciELO Periódicos Eletrônicos em Psicologia


                Comportamiento Maternal,Developmental Toxicology,Teratology,Reproductive Toxicology,Maternal Behavior,Toxicología del Desarrollo,Teratología,Toxicología Reproductiva,Toxicologia do Desenvolvimento,Teratologia,Toxicologia Reprodutiva,Comportamento Materno

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