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Prenatal Programming of Monocyte Chemotactic Protein-1 Signaling in Autism Susceptibility

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Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that involves functional and structural defects in selective central nervous system (CNS) regions, harming the individual capability to process and respond to external stimuli, including impaired verbal and non-verbal communications. Etiological causes of ASD have not been fully clarified; however, prenatal activation of the innate immune system by external stimuli might infiltrate peripheral immune cells into the fetal CNS and activate cytokine secretion by microglia and astrocytes. For instance, genomic and postmortem histological analysis has identified proinflammatory gene signatures, microglia-related expressed genes, and neuroinflammatory markers in the brain during ASD diagnosis. Active neuroinflammation might also occur during the developmental stage, promoting the establishment of a defective brain connectome and increasing susceptibility to ASD after birth. While still under investigation, we tested the hypothesis whether the monocyte chemoattractant protein-1 (MCP-1) signaling is prenatally programmed to favor peripheral immune cell infiltration and activate microglia into the fetal CNS, setting susceptibility to autism-like behavior. In this review, we will comprehensively provide the current understanding of the prenatal activation of MCP-1 signaling by external stimuli during the developmental stage as a new selective node to promote neuroinflammation, brain structural alterations, and behavioral defects associated to ASD diagnosis.

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Acknowledgements

We thank M.S. Alejandra Arreola-Triana for her support in editing this manuscript.

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  1. College of Medicine, Department of Biochemistry, Universidad Autónoma de Nuevo Leon, Monterrey, NL, Mexico

    Alberto Camacho-Morales

  2. Center for Research and Development in Health Sciences, Neurometabolism Unit, Universidad Autónoma de Nuevo Leon, San Nicolás de los Garza, Monterrey, NL, Mexico

    Alberto Camacho-Morales

  3. Tecnologico de Monterrey, Escuela de Medicina y Ciencias de La Salud and The Institute for Obesity Research, 64710, Monterrey, Mexico

    Marcela Cárdenas-Tueme

  4. Nutrition Unit, Center for Research and Development in Health Sciences, Universidad Autonoma de Nuevo Leon, 64460, Monterrey, Mexico

    Marcela Cárdenas-Tueme

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MCT and ACM wrote the manuscript and design the figures.

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Camacho-Morales, A., Cárdenas-Tueme, M. Prenatal Programming of Monocyte Chemotactic Protein-1 Signaling in Autism Susceptibility. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03940-z

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