Autism Studies and Related Medical Conditions, January 2009 - TACA

Todd, R. D. and R. D. Ciaranello (1985). "Demonstration of inter- and intraspecies
differences in serotonin binding sites by antibodies from an autistic child." Proc Natl
Acad Sci U S A 82(2): 612-6.
Serotonin (5-HT) binding sites from bovine and rat cerebral cortex membranes
share pharmacological properties that allow both to be subclassified by the same
criteria. We show here that [3H]5-HT binding sites from human cortex also
possess pharmacological properties that follow the same subclassification
scheme as for bovine and rat cortex. In addition, we show that solubilized 5-HT1
and 5-HT3 sites from all three species have an s20,w value of 3.4. Despite these
similar pharmacological and physical characteristics, we can demonstrate
antigenic differences between receptor types and species. Human 5-HT1A sites
can be distinguished from human 5-HT1B, 5-HT2, and 5-HT3 sites and from
equivalent sites in rat and bovine cortex. The anti-human 5-HT1A antibodies
were discovered in the blood of an autistic child and may have clinical or
etiologic significance for this disorder.
Todd, R. D., J. M. Hickok, et al. (1988). "Antibrain antibodies in infantile autism." Biol
Psychiatry 23(6): 644-7.
Vargas, D. L., C. Nascimbene, et al. (2005). "Neuroglial activation and
neuroinflammation in the brain of patients with autism." Ann Neurol 57(1): 67-81.
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-beta1, 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
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