RESUMO
BACKGROUND: Autism is a neurodevelopmental disorder characterized by impaired language, communication and social skills. Although genetic studies have been carried out in this field, none of the genes identified have led to an explanation of the underlying causes. Here, we have investigated molecular alterations by proteomic profiling of post mortem brain samples from autism patients and controls. The analysis focussed on prefrontal cortex and cerebellum as previous studies have found that these two brain regions are structurally and functionally connected, and they have been implicated in autism. METHODS: Post mortem prefrontal cortex and cerebellum samples from autism patients and matched controls were analysed using selected reaction monitoring mass spectrometry (SRM-MS). The main objective was to identify significantly altered proteins and biological pathways and to compare these across these two brain regions. RESULTS: Targeted SRM-MS resulted in identification of altered levels of proteins related to myelination, synaptic vesicle regulation and energy metabolism. This showed decreased levels of the immature astrocyte marker vimentin in both brain regions, suggesting a decrease in astrocyte precursor cells. Also, decreased levels of proteins associated with myelination and increased synaptic and energy-related proteins were found in the prefrontal cortex, indicative of increased synaptic connectivity. Finally, opposite directional changes were found for myelination and synaptic proteins in the cerebellum. CONCLUSION: These findings suggest altered structural and/or functional connectivity in the prefrontal cortex and cerebellum in autism patients, as shown by opposite effects on proteins involved in myelination and synaptic function. Further investigation of these findings could help to increase our understanding of the mechanisms underlying autism relating to brain connectivity, with the ultimate aim of facilitating novel therapeutic approaches.
RESUMO
BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood and adolescent development. METHODS: We carried out a multiplex immunoassay profiling analysis of serum samples from 37 individuals with a diagnosis of ASD and their matched, non-affected siblings, aged between 4 and 18 years, to identify molecular pathways affected over the course of ASDs. RESULTS: This analysis revealed age-dependent differences in the levels of 12 proteins involved in inflammation, growth and hormonal signaling. CONCLUSIONS: These deviations in age-related molecular trajectories provide further insight into the progression and pathophysiology of the disorder and, if replicated, may contribute to better classification of ASD individuals, as well as to improved treatment and prognosis. The results also underline the importance of stratifying and analyzing samples by age, especially in ASD and potentially other developmental disorders.