Autism: Neuropathology, Alterations of the GABAergic System, and Animal Models

Abstract

This chapter discusses autism neuropathology, the role of GABAergic system, the system in which neurons produce gamma-aminobutyric acid (GABA) as their output, in this disorder, and the relevance of rodent models with autistic features. With respect to the neuropathology of autism, consistent findings have emerged for the limbic system, cerebellum, and cerebral cortex. The neuropathologic data of the limbic system show increased cell packing density and smaller neurons. These observations might be explained by an arrest of normal development. As with the cholinergic system, several studies have reported a reduction in GABA function, availability, and activity in autism. A decrease in GABA receptor binding has also been shown in autism. Evidence indicates that GABA plays a role in several developmental processes, including cell migration, proliferation, and differentiation. Although the neuropathologic results in autistic subjects are revealing, animal models are essential for a better understanding of the pathophysiology, cause, and treatment of autism. The recent linkages of neuroligin (NLGN), DLX, and engrailed 2 (En2) to autism offer possibilities for animal models, particularly if introducing the relevant, specific mutations (as opposed to simple knockouts [Kos]) and can cause interesting pathology and behavior.

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