Neuroglial activation and neuroinflammation in the brain of patients with autism

TLDR

Autism is a neurodevelopmental disorder marked by impaired communication and social interaction, often accompanied by mental retardation and epilepsy, with an unknown etiology that may involve genetic, environmental, and immunological factors. The study aimed to determine whether immune‑mediated mechanisms contribute to autism’s pathogenesis. Researchers performed immunocytochemistry, cytokine protein arrays, and ELISA on brain tissues from 11 autopsied autistic patients and on fresh‑frozen tissues and CSF from 7 and 6 living patients, respectively, to assess neuroglial activation and cytokine profiles. They found an active neuroinflammatory process in cortex, white matter, and cerebellum, with marked microglial and astroglial activation and elevated MCP‑1 and TGF‑β1, and CSF showed a proinflammatory cytokine profile, indicating innate neuroimmune reactions play a pathogenic role in some autistic patients and suggesting potential therapeutic targets. An erratum was published for this article in Ann Neurol 57:304 (2005).

Abstract

Abstract Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune‐mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme‐linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh‐frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)–1 and tumor growth factor–β1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP‐1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain. Ann Neurol 2005 An Erratum has been published for this article in Ann Neurol 57: 304, 2005 .