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lüll Autism, fever, epigenetics and the locus coeruleus Mehler MF; Purpura DPBrain Res Rev 2009[Mar]; 59 (2): 388-92Some 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.|Animals[MESH]|Autistic Disorder/etiology/*physiopathology[MESH]|Epigenesis, Genetic/*physiology[MESH]|Female[MESH]|Fever/metabolism/*physiopathology[MESH]|Humans[MESH]|Locus Coeruleus/growth & development/metabolism/*physiopathology[MESH]|Nerve Net/growth & development/metabolism/physiopathology[MESH]|Neural Pathways/growth & development/metabolism/physiopathology[MESH]|Neuronal Plasticity/physiology[MESH]|Pregnancy[MESH]|Prenatal Exposure Delayed Effects/metabolism/physiopathology[MESH]|Stress, Psychological/complications/metabolism/physiopathology[MESH] |