Is autism a disease of the cerebellum? An integration of clinical and pre-clinical research - PubMed (original) (raw)

Is autism a disease of the cerebellum? An integration of clinical and pre-clinical research

Tiffany D Rogers et al. Front Syst Neurosci. 2013.

Abstract

Autism spectrum disorders are a group of neurodevelopmental disorders characterized by deficits in social skills and communication, stereotyped and repetitive behavior, and a range of deficits in cognitive function. While the etiology of autism is unknown, current research indicates that abnormalities of the cerebellum, now believed to be involved in cognitive function and the prefrontal cortex (PFC), are associated with autism. The current paper proposes that impaired cerebello-cortical circuitry could, at least in part, underlie autistic symptoms. The use of animal models that allow for manipulation of genetic and environmental influences are an effective means of elucidating both distal and proximal etiological factors in autism and their potential impact on cerebello-cortical circuitry. Some existing rodent models of autism, as well as some models not previously applied to the study of the disorder, display cerebellar and behavioral abnormalities that parallel those commonly seen in autistic patients. The novel findings produced from research utilizing rodent models could provide a better understanding of the neurochemical and behavioral impact of changes in cerebello-cortical circuitry in autism.

Keywords: autism; cerebellum.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Neural circuitry involved in cerebellar modulation of medial prefrontal cortex dopamine proposed to be affected by a developmental disconnection in autism. With the exception of inhibitory cerebellar to dentate nucleus projections, red arrows indicate glutamatergic pathways. The green arrow indicates the mesocortical dopaminergic pathway. Dotted black arrow indicates feedback loop. See text for additional details and references.

Figure 2

Figure 2

Individual examples of medial prefrontal cortex dopamine release responses evoked by electrical stimulation (black bar, 100 pulses at 50 Hz) of the dentate nucleus.

References

    1. Abou-Donia M. B., Khan W. A., Dechkovskaia A. M., Goldstein L. B., Bullman S. L., Abdel-Rahman A. (2006). In utero exposure to nicotine and chlorpyrifos alone, and in combination produces persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of adult offspring rats. Arch. Toxicol. 80, 620–631 10.1007/s00204-006-0077-1 -DOI -PubMed
    1. Allen G., Müller R. A., Courchesne E. (2004). Cerebellar function in autism: functional magnetic resonance image activation during a simple motor task. Biol. Psychiatry 56, 269–278 10.1016/j.biopsych.2004.06.005 -DOI -PubMed
    1. Amaral D. G., Schumann C. M., Nordahl C. W. (2008). Neuroanatomy of autism. Trends Neurosci. 31, 137–145 10.1016/j.tins.2007.12.005 -DOI -PubMed
    1. American Psychiatric Association. (2000). Diagnostic and Statistical Manual of Mental Disorders-IV-TR. 4th Edn Washington, DC: American Psychiatric Association
    1. Amir R. E., Van den Veyver I. B., Wan M., Tran C. Q., Francke U., Zoghbi H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185–188 10.1038/13810 -DOI -PubMed

LinkOut - more resources