RESUMO
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112). Findings: Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034). Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD.
Assuntos
Ácidos Araquidônicos/sangue , Transtorno Autístico/sangue , Agonistas de Receptores de Canabinoides/sangue , Endocanabinoides/sangue , Alcamidas Poli-Insaturadas/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Group housing is highly important for social animals. However, it can also give rise to aggression, one of the most serious welfare concerns in laboratory mouse husbandry. Severe fighting can lead to pain, injury and even death. In addition, working with animals that are severely socially stressed, wounded or singly-housed as a result of aggression may compromise scientific validity. Some general recommendations on how to minimize aggression exist, but the problem persists. Thus far, studies attempting to find solutions have mainly focused on social dominance and territorial behavior, but many other aspects of routine housing and husbandry that might influence aggressive behavior have been overlooked. The present way of housing laboratory mice is highly unnatural: mice are prevented from performing many species-typical behaviors and are routinely subjected to painful and aversive stimuli. Giving animals control over their environment is an important aspect of improving animal welfare and has been well-studied in the field of animal welfare science. How control over the environment influences aggression in laboratory mice, however, has not been closely examined. In this article, we challenge current ways of thinking and propose alternative perspectives that we hope will lead to an enhanced understanding of aggression in laboratory mice.