Journal
BRAIN RESEARCH REVIEWS
Volume 59, Issue 2, Pages 388-392Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainresrev.2008.11.001
Keywords
Gene-environmental interaction; Prenatal stressor; Neuromodulator; Sensorimotor processing; Homeostatic signal; Developmental critical period; Imprinted gene; Pharmacoepigenomic agent
Categories
Funding
- National Institutes of Health [RO1 MH66290, RO1 NS38902]
- Roslyn and Leslie Goldstein
- Mildred and Bernard H. Kayden
- F. M. Kirby
- Alpern Family
- Rosanne H. Silberman Foundations
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH066290] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS038902] Funding Source: NIH RePORTER
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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. (C) 2008 Elsevier B.V. All rights reserved.
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