Abstract
Autism spectrum disorder (ASD) is manifested by abnormal cell numbers and patches of gene expression disruption in higher-order brain regions. Here, we investigated whether layer-specific changes in glia/neuron ratios (GNR) characterize patches in the dorsolateral prefrontal cortex (DL-PFC) of children with ASD. We analyzed high-resolution digital images of postmortem human brains from 11 ASD and 11 non-ASD children obtained from the Autism Study of the Allen Human Brain Atlas. We found the GNR is overall reduced in the ASD DL-PFC. Moreover, layers II-III belonging to patches presented a lower GNR in comparison with layers V-VI. We here provide a new insight into how brain cells are arranged within patches that contributes to elucidate how neurodevelopmental programs are altered in ASD.
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The authors are thankful to the Allen Institute for Brain Sciences and the organizers of the Autism Study within the Allen Human Brain Atlas database for generously providing case studies to the neuroscientific community.
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This work was supported by Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES) and by Grant NS107131 (NIH/NINDS).
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LR and FF: Designed the study. LR, JQ, CC, SS, EN, LC and LS: Performed image processing, cell quantification, statistical analyses and prepared figures. LR, FF and VMC: Wrote the final paper receiving inputs from all authors. All authors contributed to the article and approved the submitted version.
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This work uses data available from the Autism Study- Allen Human Brain atlas, an open database compiled by the Allen Institute for Brain Sciences (access at: https://human.brain-map.org/ish/search/). This work did not involve any human or animal model experimentation, nor clinical trials or direct usage of brain tissues. Instead, the present work is an in-silico analysis of digital images previously obtained and compiled by the database organizers. Permission for usage in academic research of the downloadable content, including these images, is explicit and encouraged in https://alleninstitute.org/legal/terms-use/. As it is stated in the Allen Institute Legal Terms, no further approval is requested for the usage of this data. The database organizers obtained the original histological material, with all due approvals, from the National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders (Baltimore, MD) under contracts N01-HD-4-3368 and N01-HD-4-3383, the Brain and Tissue Bank for Developmental Disorders (Miami, FL), Autism Tissue Program (Princeton, NJ) and Harvard Brain Tissue Resource Center (Belmont, MA). This information is disclosed in http://help.brain-map.org/display/humanbrain/Documentation. The ethics committee for human research at the Santos Dumont Institute- Brazil (CEP-ISD) waived the need of any further approval. The study abides by the Declaration of Helsinki principles.
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Rabelo, L.N., Queiroz, J.P.G., Castro, C.C.M. et al. Layer-Specific Changes in the Prefrontal Glia/Neuron Ratio Characterizes Patches of Gene Expression Disorganization in Children with Autism. J Autism Dev Disord 53, 3648–3658 (2023). https://doi.org/10.1007/s10803-022-05626-8
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DOI: https://doi.org/10.1007/s10803-022-05626-8