Cellular and Molecular Biology of Autism Spectrum Disorders

Immunoexcitotoxicity as a Central Mechanism of Autism Spectrum Disorders

Author(s): Russell L. Blaylock

Pp: 47-72 (26)

DOI: 10.2174/978160805196011001010047

* (Excluding Mailing and Handling)

Abstract

Autism has undergone a tremendous amount of study, and a number of often seemingly unconnected disorders have been disclosed. Yet, despite an enormous amount of study, no central mechanism to explain the causation of this syndrome or why it affects only a subset of children has come forth. In this chapter I propose such a central mechanism that explains a great number of biochemical, histological, neurodevelopmental and systemic dysfunctions, as well as behavioral findings in autism spectrum disorders (ASD). Since the discovery of excitotoxicity by Olney in 1968, neuroscientists have determined that not only is glutamate a neurotransmitter, but it is the most abundant neurotransmitter in the brain, exceeding the more traditional neurotransmitters combined. Recent studies have also shown that glutamatergic receptors (GluRs) interact with other receptors, not only neurotransmitters, but also immune receptors, in a way that can alter their sensitivity. Chronic brain inflammation is known to dramatically enhance the sensitivity of N-methyl-D-aspartic acid (NMDA) and α- amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) type GluRs and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity and abnormal synaptic and dendritic physiology over a prolonged period. Importantly, neuroscience studies have clearly shown that sequential systemic immune stimulation can not only activate the brain ’ s immune system, microglia and astrocytes, but that there occurs an amplified response to both subsequent stimulation, either systemic or within the CNS. The ASD child is exposed to such sequential immune stimulation via a growing number of vaccines, recurrent infections, chemical toxins and persistent viral infections.

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