AI Article Synopsis
- Autism spectrum disorder (ASD) includes a range of neurodevelopmental conditions with core behavioral symptoms critical for diagnosis, linked to altered dopamine (DA) neurotransmission in the striatum.
- Research in a mouse model with elevated eukaryotic initiation factor 4E (eIF4E) expression shows that this increase leads to behavioral inflexibility and impaired DA release in the striatum.
- These impairments stem from defective nicotinic receptor signaling affecting calcium dynamics in dopaminergic axons, highlighting the complex interactions between eIF4E, DA neurotransmission, and ASD symptoms, which could guide future therapies.
Article Abstract
Autism spectrum disorder (ASD) consists of diverse neurodevelopmental conditions where core behavioral symptoms are critical for diagnosis. Altered dopamine (DA) neurotransmission in the striatum has been suggested to contribute to the behavioral features of ASD. Here, we examine DA neurotransmission in a mouse model of ASD characterized by elevated expression of eukaryotic initiation factor 4E (eIF4E), a key regulator of cap-dependent translation, using a comprehensive approach that encompasses genetics, behavior, synaptic physiology, and imaging. The results indicate that increased eIF4E expression leads to behavioral inflexibility and impaired striatal DA release. The loss of normal DA neurotransmission is due to a defect in nicotinic receptor signaling that regulates calcium dynamics in dopaminergic axons. These findings provide a mechanistic understanding of ASD symptoms and offer a foundation for targeted therapeutic interventions by revealing the intricate interplay between eIF4E, DA neurotransmission, and behavioral flexibility.
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| http://dx.doi.org/10.1016/j.celrep.2024.114997 | DOI Listing |
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