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Brain Res Rev. 2009 Mar;59(2):388-92. doi: 10.1016/j.brainresrev.2008.11.001. Epub 2008 Nov 24.

Autism, fever, epigenetics and the locus coeruleus.

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  • 1Institute for Brain Disorders and Neural Regeneration, The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. mehler@aecom.yu.edu

Abstract

Some children with autism spectrum disorders (ASD) exhibit improved behaviors and enhanced communication during febrile episodes. We hypothesize that febrigenesis and the behavioral-state changes associated with fever in autism depend upon selective normalization of key components of a functionally impaired locus coeruleus-noradrenergic (LC-NA) system. We posit that autistic behaviors result from developmental dysregulation of LC-NA system specification and neural network deployment and modulation linked to the core behavioral features of autism. Fever transiently restores the modulatory functions of the LC-NA system and ameliorates autistic behaviors. Fever-induced reversibility of autism suggests preserved functional integrity of widespread neural networks subserving the LC-NA system and specifically the subsystems involved in mediating the cognitive and behavioral repertoires compromised in ASD. Alterations of complex gene-environmental interactions and associated epigenetic mechanisms during seminal developmental critical periods are viewed as instrumental in LC-NA dysregulation as emphasized by the timing and severity of prenatal maternal stressors on autism prevalence. Our hypothesis has implications for a rational approach to further interrogate the interdisciplinary etiology of ASD and for designing novel biological detection systems and therapeutic agents that target the LC-NA system's diverse network of pre- and postsynaptic receptors, intracellular signaling pathways and dynamic epigenetic remodeling processes involved in their regulation and functional plasticity.

PMID:
19059284
[PubMed - indexed for MEDLINE]
PMCID:
PMC2668953
Free PMC Article
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