Autism, fever, epigenetics and the locus coeruleus

作者：Mehler Mark F^*; Purpura Dominick P

来源：Brain Research Reviews, 2009, 59(2): 388-392.

DOI：10.1016/j.brainresrev.2008.11.001

• Gene-environmental interaction
• Prenatal stressor
• Neuromodulator
• Sensorimotor processing
• Homeostatic signal
• Developmental critical period
• Imprinted gene
• Pharmacoepigenomic agent

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.

• 出版日期2009-3