A new study carried out by researchers from Northwestern University Feinberg School of Medicine and David Geffen School of Medicine at UCLA has now provided a novel way to combat autism.
Fragile X syndrome (FXS) is a genetic disorder, which more frequently occurs in males than in females. Although it's usually not associated with life-threatening health concerns, it can lead to intellectual disability, behavioral and learning problems, and physical characteristics. About 15-20% of people with FXS show autistic-type behaviors. FXS is the most common known single gene cause of autism spectrum disorder (ASD).
The exact cause of ASD has been fully understood. But it's believed that the condition results from abnormalities in the brain. Various factors may be involved in the pathogenesis of ASD, such as heredity, heredity, genetics, medical problems, and environmental factors. Many genetic variants have been identified to increase the risk of ASD, but most of them are rare.
FXS has been modeled in mice using molecular genetic manipulation. These mouse models can help researchers study ASD.
Using these mouse models, the researchers found that sensory perturbations, which are a core symptom of FXS, could result from increased intracellular chloride in neurons during early development. When the researchers inhibited the juvenile chloride co-transporter NKCC1, the chloride imbalance was rectified and synapse development was restored. Analyses of protein concentrations revealed that NKCC1 inhibition led to remodeling of the proteome.
NKCC1 is a membrane transport protein that is encoded by the gene SLC12A2
in humans. It transports chloride and other ions across the cell membrane.
Taken together, these results suggest that chloride imbalance might be involved in the pathogenesis of FXS and normalizing chloride might be a way to treat FXS and ASD.
Details of the study have been published in a paper titled "Critical period inhibition of NKCC1 rectifies synapse plasticity in the somatosensory cortex and restores adult tactile response maps in fragile X mice," appearing in the journal Molecular Psychiatry.
According to Anis Contractor at Northwestern University Feinberg School of Medicine, who is the corresponding author of the study, mouse brain development is not completely the same as human brain development but there are similarities between them. Many patients with FXS have sensory problems that may ultimately lead to social isolation.
Previous research by Contractor's team emphasized the role of intracellular chloride in FXS. The current study furthered the understanding of this role. More research is needed to explore the therapeutic potential of correcting chloride in FXS and ASD. Furthermore, the study may also have profound applications in other neurodevelopmental diseases.