Progress Toward Treatments for Synapic Defects in Autism
Rodent models of ASD, mainly imitating the genetic abnormalities identified in patients such as loss-of-function mutations, mis-sense point mutations, and gene duplications, have contributed largely to the understanding of the circuit, synaptic, and behavioral basis of autism spectrum disorder. Some mouse models with ASD demonstrated core autistic symptoms such as social impairment and repetitive behavior, even though they vary broadly besides co-morbidities and in alternations in inhibitory and excitatory synaptic transmission in certain neuronal circuits.
In looking deeper in the ASD mouse models’ synaptic modifications, Wang examined spine density changes in two characterized mouse gene-duplication models of ASD, particularly the MECP2 duplication as well as human chromosome 15q11-13 duplication models. They discovered in the mouse’s sematosensory cortex that 15q11-13 duplication mainly affects spine formation at a month of postnatal development, while MECP2 duplication is interfering with spine spruning at 3 months without really impacting spine formation. It is vital to induce genetic modifications with cell-type and spatial-temporal specificity to study the function of ASD genes in certain circuits and at particular time points during development.
The review by Jiang and Hulbert talks about the presently available assays and tools for studying ASD in rodent models, reviewing fully the genetic tools available via the cre/LoxP system for inducing genetic alternations in certain cell types and brain regions with temporal control.
Newer diagnostic tools and treatments are becoming available thanks to advances at circuit, modecular, and genetic levels.