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Universidade Federal Do Rio Grande Do Sul Faculdade De Medicina Programa De Pós-graduação Em Saúde Da Criança E
| Content Provider | Semantic Scholar |
|---|---|
| Author | Doutorado, Tese De Baronio, Diego Moura Riesgo, Rudimar Dos Santos Silveira, Patricia Pelufo Gama, Clarissa Severino Bauer, Moisés Evandro Baronio, Mauro Santos, Mariane Ferreira Dos |
| Copyright Year | 2014 |
| Abstract | Introduction: Autism spectrum disorder (ASD) is primarily characterized by impaired social interaction and communication, and by restricted repetitive behaviors and interests. Alterations in different neurotransmitter systems, such as serotonergic, GABAergic and glutamatergic have been studied and reported in ASD. Surprisingly, the histaminergic system has received less attention and few studies are available on the literature about histamine and ASD. In addition, ligands of histamine receptor 3 (H3R) are considered potential therapeutic agents for the treatment of different brain disorders and cognitive impairments, but its effects on autistic-like features have not been evaluated. Objectives: The objective of this study was to evaluate the actions of ciproxifan (CPX), an H3R inverse agonist, on the animal model of autism induced by prenatal exposure to valproic acid (VPA) and to measure the concentration of histamine and the H3R and H4R mRNA levels in different brain structures of this model. In addition, to investigate the role of H3R in sociability and stereotypic behavior. Methods: Swiss mice were prenatally exposed to VPA on embryonic day 11 and assessed for social behavior, nociceptive threshold and repetitive behavior at 50 days of life after treatment with CPX. After the behavioral tests, animals were killed by exsanguination after being anesthetized with isoflurane. Cerebral cortex, striatum and hippocampus were removed, frozen in liquid nitrogen and stored at -80°C for quantification of H3R and H4R mRNA by qPCR and histamine content by HPLC analysis. H3R KO and WT C57BL/6J mice, at 50 days of life, were used in the three-chamber test and marble burying test to determine the role of H3R in sociability stereotypic behavior. Results: The VPA group presented lower sociability index compared to VPA animals that were treated with CPX. Compared to the Control group, VPA animals presented a significantly higher nociceptive threshold, and treatment with CPX was not able to modify this parameter. In the marble burying test, the number of marbles buried by VPA animals was consistent with markedly repetitive behavior. VPA animals that received CPX buried a reduced amount of marbles. A significant increase in H3R mRNA, as well as higher concentration of histamine were detected in striatal samples from the VPA mice. H3R might influence the search for social novelty, a feature that is impaired in ASD, as H3R KO mice displayed abnormal behavior when tested for this parameter in the three chambers test. Conclusions: In summary, an acute dose of CPX is able to revert sociability deficits and stereotypies present in the VPA model of autism. In addition, this is the first report of abnormalities in the histaminergic system of this model. These findings have the potential to help the investigations of both the molecular underpinnings of ASD and of possible treatments to ameliorate the ASD symptomatology, although more research is still necessary to corroborate and expand this initial data. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.lume.ufrgs.br/bitstream/handle/10183/131172/000979716.pdf?sequence=1 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
