Autism Susceptibility自闭症的易感性.ppt

Why does ASD susceptibility matter Early detection of ASD genes (such as SHANK2) Critical Period Early intervention: therapy, special education, home enrichment, pharmacological approaches Children with same mutation but different home life vary in cognitive function Susceptibility SHANK2 Mutations without ASD At risk for having ASD children Environmental factors /nature/journal/v486/n7402/extref/nature11208-s6.mov /nature/journal/v486/n7402/extref/nature11208-s7.mov /nature/journal/v486/n7402/extref/nature11208-s8.mov * Use it or lose it! * Autism Susceptibility Autism Neuro-developmental disorder Impaired communication, social interaction, empathy, repetitive behavior, restricted interests, ADHD Typical onset/diagnosis at 3 (can be as late as 14) Diagnosis vs onset 1/110 children diagnosed 4:1 boys to girl affected Spectrum: low to high cognitive function Autism, PDD, Rett’s disorder, child disintegrative disorder, and Asperger’s disorder Pediatrics (2004) 113:472-486 Causation Causes: Unknown Genetic: Susceptibility genes (HOXA1, FOXp2, DBH, MeCP2, NLGN3, NLGN4, NRN1, FMR1, SHANK2, TAOK2 Environmental: Diet (nutrient deficiencies, high fructose corn syrup, , toxic environment (mercury), Thimerosal (maybe), age of parents, acetaminophen Immunological factors: defective placenta, immature BBB, immune response of mother to infection during pregnancy Journal of Immunotoxicology, 2011; 8(1): 68–79 Causation Single factor vs Multifactor Development vs Plasticity Developmental Factors TAOK2 Impaired dendrite formation Abnormal connectivity (hyper hypo connectivity) Nature Neuro, 2012; 15(7): 1022-1033 Autism and Dendrite Development Sign up for Neurobiology of Disease next semester!!!! Covering this AND… Parkinson’s, Alzheimer’s, Fragile X, MS, ALS, and MORE! Causation Single factor vs Multifactor Development vs Plasticity Synaptic Plasticity and Transmission NMDA activation or CAMKII activation leads to AMPA trafficking Synapse Formation PSD Scaff