Immune system activity in the central nervous system (CNS) has been implicated in numerous neuroinflammatory diseases. Over the past decade, however, Jonathan Kipnis has found evidence that mice with immune deficiencies also exhibit cognitive impairments.

Disruption in the number and function of brain synapses — the connections between neurons — is a central feature in the development of autism and associated cognitive disabilities. Although our understanding of how brain development differs in autism is not complete, an early overgrowth of neurons and synapses, as well as a failure to prune inappropriate synapses, has been observed in the brains of children with autism and in autism mouse models. At the molecular level, overproduction of key synaptic proteins may contribute to the atypical neural and synaptic growth in autism.

Despite the diversity and the rising prevalence of diagnosed cases of autism, the etiology of the disorder remains an open question. Efforts to understand the pathophysiology of autism have focused on genetic factors. However, considering the tremendous diversity of autism types, it seems likely that the causes of autism spectrum disorders are numerous and perhaps overlapping.

One of the most common genetic causes of autism is the loss or duplication of a small region on human chromosome 16 known as 16p11.2. These genetic changes account for only about 1 percent of all cases of autism, but when present, they frequently result in the disorder.

Inflammation during pregnancy has been suggested as a possible contributing factor in the development of autism spectrum disorders in children. A replica of this phenomenon, called the maternal immune activation (MIA) model, is used to study inflammation-induced behavioral changes in rodents. Identification of key immune components in the MIA model may lead to a better understanding of underlying causes of autism.

Shared exposure to environmental factors appears to have a more prominent role in autism than genetics does. Polybrominated diphenyl ethers (PBDEs) are members of an important group of chemicals used in plastics, textiles, furniture and electronic devices. The global production of PBDEs has reached approximately 148 million pounds per year. PBDEs are used as flame retardants in plastics, to which they do not bind chemically. They can thus leach from polymers and pervasively accumulate in the built environment and ecosystem.

One of the most important steps in postnatal brain development is the formation of the connections between neurons, known as synapses. These connections establish the neural circuits that control behavior. NMDA receptors are key molecules in the development and functioning of synapses that use the neurotransmitter glutamate.

The brain consists of two main types of cells, neurons and glia. Although neurons have been extensively studied, the contribution of glial cells to autism is not well understood. To address this deficit in knowledge, Erik Ullian and his colleagues proposed to investigate the developmental profile and functional properties of a special type of glial cell called an oligodendrocyte (OC), a specialized cell that enwraps axons with an insulating sheath that is essential for proper brain function and the transmission of signals among brain regions.

The most prevalent genetic form of mental retardation, fragile X syndrome, is a single-gene disorder leading to loss of the RNA-binding protein FMRP. Loss of FMRP results in improper messenger RNA (mRNA) translation at synapses — the junctions between nerve cells — synaptic dysfunction, impaired cognitive function and autism-associated behaviors. To investigate the role of synaptic mRNA translation in normal synapse development, mRNAs and their functions need to be identified. While studies have examined the mRNA populations localized to synapses in rodent model systems, the identity of mRNAs at human synapses is unknown.

Duplication of a small segment of human chromosome 7 has been found in some children with autism. Lucy Osborne and her colleagues at the University of Toronto aim to understand the effects of duplication of this region, 7q11.23, on the growth and function of the brain. They plan to study this using a mouse model with a similar duplication.