title: Immature Neurons and Radial Glia, But Not Astrocytes or Microglia, Are Altered in Adult Cntnap2 and Shank3 Mice, Models of Autism.
abstract: 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 that display autism-like phenotypes, Cntnap2-/-and Shank3+/ΔCtransgenic 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 with 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.
authors: Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540; Department of Psychology, Princeton University, Princeton, New Jersey 08544.
authors: Elise C
authors: EC
authors: Cope
authors: Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540; Department of Psychology, Princeton University, Princeton, New Jersey 08544.
authors: Brandy A
authors: 0000-0003-4692-3399
authors: BA
authors: Briones
authors: Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540; Department of Psychology, Princeton University, Princeton, New Jersey 08544.
authors: Adam T
authors: 0000-0001-7712-5053
authors: AT
authors: Brockett
authors: Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540; Department of Psychology, Princeton University, Princeton, New Jersey 08544.
authors: Susana
authors: S
authors: Martinez
authors: Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540; Department of Psychology, Princeton University, Princeton, New Jersey 08544.
authors: Pierre-Antoine
authors: 0000-0003-2918-0909
authors: PA
authors: Vigneron
authors: Princeton Neuroscience Institute, Princeton University , Princeton, New Jersey 08540.
authors: Maya
authors: 0000-0003-4334-3188
authors: M
authors: Opendak
authors: Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540; Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544.
authors: Samuel S-H
authors: 0000-0002-0490-9786
authors: SS
authors: Wang
authors: Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08540; Department of Psychology, Princeton University, Princeton, New Jersey 08544.
authors: Elizabeth
authors: E
authors: Gould
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001321:Autistic Disorder / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology
chemical_list: C568163:CNTNAP2 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C492356:Shank3 protein, mouse
keywords: astrocytes; autism; microglia; neurogenesis; radial glia