Dendrites in autism spectrum disorders

Abstract

Autism spectrum disorders (ASDs), including classic autism and various syndromic ASDs, are a diverse group of complex developmental disability characterized by social impairments, communication difficulties, and restricted, repetitive, and stereotyped patterns of behavior. As many as 1 in 80 children in the United States are affected by some form of ASDs, an alarming statistics. The core symptoms of autism are considered due to under-connectivity among the brain regions participating in cortical networks, a consequence of complex pathological gene-environmental interactions. Recent investigations on ASD susceptible genes and environmental risk factors such as exposure to environmental toxins, perinatal or postnatal infections, obstetric factors, and medications have provided greater clarity to the clinical and biological complexity of ASDs. This chapter provides a comprehensive review to illustrate that most genetic and environmental risks for ASDs cause dendritic abnormalities underlying brain under-connectivity. Rodent models harboring mutated ASD susceptible genes or exposed to environmental risk factors have helped delineate molecular pathways leading to autism-like dendritic abnormalities, and the findings can be further validated by human neuropathological studies. It is intriguing to consider dendritic abnormalities as main pathological substrates of autism; targeting specific molecular pathways driving such abnormalities could lead to realization of the ideal of providing “precision medicine” to autistic children. This review also illustrates that the immune system with its myriad of cells and mediators has a great impact on the developing brain, and our “microglia hypothesis” proposes that microglia play a pivotal role in mediating environmental and genetic effects on dendritic pathology in autism.