4.6 Article

Increasing astrogenesis in the developing hippocampus induces autistic-like behavior in mice via enhancing inhibitory synaptic transmission

期刊

GLIA
卷 70, 期 1, 页码 106-122

出版社

WILEY
DOI: 10.1002/glia.24091

关键词

astrogenesis; autistic-like behavior; early development; excitatory-inhibitory balance; GABAergic synaptic transmission; hippocampus

资金

  1. National Key Research and Development Program [2019YFA0801900]
  2. National Natural Science Foundation of China [81971139, 81821091, 81770839, 82171340]
  3. Fundamental Research Funds for the Central Universities [2019FZA7004]

向作者/读者索取更多资源

Autism spectrum disorder (ASD) is characterized by impaired social communication and rigid behaviors, and abnormal synapse development and E/I imbalance may contribute to its pathogenesis. Astrocytes play a crucial role in synaptic formation and function, and targeting altered GABAergic neurotransmission represents a promising therapeutic strategy for ASD.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic-like behavior in mice and a concurrent decreased E/I ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic-like behavior and restores the E/I balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.

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