Cerebellum and Autism

Excerpt

The accumulation of published literature clearly indicates that the cerebellum is involved in the pathology of autism [1‐3]. As to whether cerebellar pathology is primal or only part of an important brain circuitry involved in autism, the data are incomplete. What is clearly new and relevant to the etiology of autism is that cerebellar function is not limited to motor coordination but involves processing of cognition which is at the heart of autistic pathology [1, 4]. Fatemi et al. [5] recently reviewed the existing literature with respect to the pathological involvement of cerebellum in autism. The preponderance of evidence supports the involvement of this important brain area in etiology of autism. Recent supportive literature links developmental cerebellar pathology with decreased prefrontal dopamine transmission [3] and autistic behavior [6] in various animal models of autism. In a series of experiments, Rogers et al. [3] showed that despite having different cerebellar abnormalities, both the Lurcher and fragile X mental retardation 1 mutant mice exhibited abnormalities involving the cerebellar–prefrontal circuitry which resulted in abnormal dopamine transmission that underlie cognitive deficits in both mutant mouse models reminiscent of autistic phenotype. By the same token, Tsai et al. [6] showed that loss of tuberous sclerosis complex 1 protein in mouse cerebellar Purkinje cells in both heterozygous and homozygous mutants results in autistic behavior. Treatment with the mTOR inhibitor, rapamycin, prevented both biochemical and behavioral deficits, further supporting a cerebellar contribution to the autistic etiology [6]. …