Autism spectrum disorder (ASD) is often associated with cognitive deficits and excessive anxiety. Neuroimaging studies have shown atypical structure and neural connectivity in the hippocampus, medial prefrontal cortex (mPFC) and striatum, regions associated with cognitive function and anxiety regulation. Adult hippocampal neurogenesis is involved in many behaviors that are disrupted in ASD including cognition, anxiety and social behaviors. Additionally, glial cells, such as astrocytes and microglia, are important for modulating neural connectivity during development, and glial dysfunction has been hypothesized to be a key contributor to the development of ASD. Cells with astroglial characteristics are known to serve as progenitor cells in the developing and adult brain. Here, we examined adult neurogenesis in the hippocampus, as well as astroglia and microglia in the hippocampus, mPFC and striatum of two models which display autism-like phenotypes, Cntnap2-/- and Shank3+/ΔC transgenic mice. We found a substantial decrease in the number of immature neurons and radial glial progenitor cells in the ventral hippocampus of both transgenic models compared to wild-type controls. No consistent differences were detected in the number or size of astrocytes or microglia in any other brain region examined. Future work is needed to explore the functional contribution of adult neurogenesis to autism-related behaviors as well as to temporally characterize glial plasticity as it is associated with ASD.
Significance Statement: Autism spectrum disorder (ASD) is a heterogeneous developmental condition that is estimated to affect one in sixty-eight children under the age of eight in the United States. Postmortem studies suggest that both neurons and glia may be compromised in ASD, but few studies have explored neural and glial plasticity across relevant mouse models. We found a decrease in adult neurogenesis in the ventral hippocampus, a brain region important for anxiety and stress regulation, in two autism mouse models compared to wild-type controls. However, we found no differences in markers of glial dysregulation across autism mouse models in the hippocampus, mPFC or striatum, suggesting that persistent abnormalities in glia in these brain regions are not necessary for the ASD behavioral phenotype.
Authors report no conflict of interest.
This work was supported by a grant from the Nancy Lurie Marks Family Foundation.