RESUMO
Autism spectrum disorder (ASD) is a diverse group of neurodevelopmental conditions with complex origins. Individuals with ASD present various neurobiological abnormalities, including an altered immune response in the central nervous system and other tissues. Animal models like the C58/J inbred mouse strain are used to study biological characteristics of ASD. This strain is considered an idiopathic autism model because of its demonstrated reduced social preference and repetitive behaviours. Notably, C58/J mice exhibit alterations in dendritic arbour complexity, density and dendritic spines maturation in the hippocampus and prefrontal cortex (PFC), but inflammatory-related changes have not been explored in these mice. In this study, we investigated proinflammatory markers in the hippocampus and PFC of adult male C58/J mice. We discovered elevated levels of interferon gamma (IFN-γ) and monocyte chemoattractant protein 1 (MCP-1) in the hippocampus, suggesting increased inflammation, alongside a reduction in the anti-inflammatory enzyme arginase 1 (ARG1). Conversely, the PFC displayed reduced levels of TNF-α and MCP-1. Microglial analysis revealed higher levels of transmembrane protein 119 (TMEM119) and increased microglial density in a region-specific manner of the autistic-like mice, particularly in the PFC and hippocampus. Additionally, an augmented expression of the fractalkine receptor CX3CR1 was observed in the hippocampus and PFC of C58/J mice. Microglial morphological analysis shows no evident changes in the hippocampus of mice with autistic-like behaviours versus wild-type strain. These region-specific changes can contribute to modulate processes like inflammation or synaptic pruning in the C58/J mouse model of idiopathic autism.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Camundongos , Masculino , Animais , Transtorno Autístico/metabolismo , Transtorno do Espectro Autista/metabolismo , Microglia/metabolismo , Camundongos Endogâmicos , Córtex Pré-Frontal/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Autism spectrum disorder (ASD) has a broad range of neurobiological characteristics, including alterations in dendritic spines, where approximately 90% of excitatory synapses occur. Therefore, changes in their number or morphology would be related to atypical brain communication. The C58/J inbred mouse strain displays low sociability, impaired communication, and stereotyped behavior; hence, it is considered among the animal models suitable for the study of idiopathic autism. Thus, this study aimed to evaluate the dendritic spine differences in the hippocampus and the prefrontal cortex of C58/J mice. We found changes in the number of spines and morphology in a brain region-dependent manner: a subtle decrease in spine density in the prefrontal cortex, higher frequency of immature phenotype spines characterized by filopodia-like length or small morphology, and a lower number of mature phenotype spines with mushroom-like or wide heads in the hippocampus. Moreover, an in silico analysis showed single nucleotide polymorphisms (SNPs) at genes collectively involved in regulating structural plasticity with a likely association with ASD, including MAP1A (Microtubule-Associated Protein 1A), GRM7 (Metabotropic Glutamate Receptor, 7), ANKRD11 (Ankyrin Repeat Domain 11), and SLC6A4 (Solute Carrier Family 6, member 4), which might support the relationship between the C58/J strain genome, an autistic-like behavior, and the observed anomalies in the dendritic spines.
RESUMO
Autism spectrum disorder (ASD) has been associated to atypical neuronal connectivity in the prefrontal cortex (PFC) and the hippocampus, in part, due to an alteration in neuroplasticity processes such as dendritic remodeling. Moreover, it has been proposed that abnormal cytoskeletal dynamics might be underlying the disrupted formation and morphology of dendrites in the ASD brain. Hence, we performed an analysis of the complexity of dendritic arborization of the pyramidal neurons localized in the layer II/III of the PFC and the CA1 region of the hippocampus in the autistic-like mouse strain C58/J, which has previously demonstrated neuronal cytoskeleton anomalies. We found differences in length, number and branching pattern of dendrites of the pyramidal neurons from both structures of C58/J strain. These data suggest a lower dendritic arborization complexity that could be involved with the characteristic autistic-like behaviors displayed in C58/J mice.