Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

Abstract

In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was seen throughout superior temporal cortex (primary auditory cortex), fusiform cortex (face recognition center), pons/midbrain and cerebellum in postmortem brains from ASD patients but not control brains. We found significant increases in both nestin and CD34, which are markers of angiogenesis localized to pericyte cells and endothelial cells, respectively. This labeling profile is indicative of splitting (intussusceptive), rather than sprouting, angiogenesis indicating the blood vessels are in constant flux rather than continually expanding.

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Acknowledgments

NYU Challenge Grant 2014–2015 (Azmitia) and NIMH R01MH083862-05 (Boldrini) provided the necessary support for this work. Dr. Jerzy Wegiel for his invaluable advice and support during this work and also for contributing human postmortem tissue. Dr. Jane Pickett for her encouragement throughout this project and her help in obtaining postmortem tissue from the Autism Tissue Program. Dr. H.R. Zielke for providing postmortem brain tissue from the NICHD brain bank and, in particular, for making available samples from a autism donor who died from serotonin syndrome. Finally, helpful technical work was supplied by Victoria Lee, Amritpal Saini, Hanna Chen, Pooja P Kothari and Gordon Jiang.

Author Contributions

EA participated in all aspects of the study from concept to drafting the manuscript; ZS coordination of the study and performed the measurement; participated in the design and interpretation of the data; performed the statistical analysis; helped to draft the manuscript; MA coordination of the study and performed the measurement; helped to draft the manuscript; MB participated in the design of the study and performed the statistical analysis; PW participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.

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Azmitia, E.C., Saccomano, Z.T., Alzoobaee, M.F. et al. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum. J Autism Dev Disord 46, 1307–1318 (2016). https://doi.org/10.1007/s10803-015-2672-6

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Keywords

  • Intussusceptive
  • Pericytes
  • Endothelial
  • Nestin
  • CD34
  • Superior temporal cortex