Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects social communication, language development, and behavior. Research has identified over 70 genes potentially linked to autism, but scientists are still investigating how each gene contributes to the condition.
One such gene is Astrotactin 2 (ASTN2). In 2018, researchers at Rockefeller University discovered that mutations in the ASTN2 gene disrupted connections in the cerebellum, contributing to neurodevelopmental disorders. Now, a new study suggests that the complete absence of this gene may lead to key autism-related behavioral changes.
Behavioral Changes and Autism-Like Traits
A study published in PNAS found that mice lacking the ASTN2 gene exhibited four significant behavioral differences compared to their wild-type counterparts:
- They vocalized less and had weaker communication skills.
- Their social interactions were reduced, and they struggled to adapt to new environments.
- They exhibited hyperactive behaviors.
- Repetitive movements (stereotypical behaviors) increased significantly.
These traits closely resemble core characteristics observed in individuals with autism. Lead author Michalina Hanzel explains, “Deficits in communication, social withdrawal, hyperactivity, and repetitive behaviors are hallmarks of autism. We observed strikingly similar tendencies in mice lacking the ASTN2 gene.”
The Cerebellum’s Role Beyond Motor Control
Traditionally, the cerebellum has been associated mainly with motor functions such as balance and coordination. However, growing evidence suggests that it also plays a critical role in language, cognition, and social behavior.
Mary E. Hatten, a neuroscientist at Rockefeller University, highlights the significance of this research:
“These findings reinforce the idea that the cerebellum contributes to cognitive functions beyond motor control.”
Experiments on Mice: Key Findings
To analyze behavioral differences, researchers conducted a series of experiments comparing ASTN2-deficient mice with wild-type mice:
- Communication Test:
- When separated from their mothers, normal baby mice used complex ultrasonic calls to seek attention, whereas ASTN2-deficient mice produced fewer and simpler calls.
- This finding mirrors language development difficulties commonly observed in individuals with autism.
- Social Interaction Test:
- Wild-type mice preferred interacting with unfamiliar mice, whereas ASTN2-deficient mice spent more time with familiar ones.
- This behavior aligns with the tendency of autistic individuals to avoid unfamiliar social interactions.
- Hyperactivity and Repetitive Behaviors:
- ASTN2-deficient mice covered longer distances in open spaces and engaged in repetitive actions like circling.
- These behaviors resemble the hyperactivity and repetitive movements frequently observed in autism.
Structural Changes in the Brain
Upon examining the brains of ASTN2-deficient mice, researchers identified several small but potentially significant structural and physiological changes in the cerebellum:
- Increased Purkinje cell density: These neurons, essential for cerebellar signaling, displayed an unusually high number of dendritic spines.
- Altered neural connections: Communication between the cerebellum and other brain regions appeared to be disrupted.
Hatten explains, “Even small structural changes can significantly alter brain signaling, potentially leading to autism-related behaviors.”
Future Research on Human Cells
The next phase of research will involve analyzing cerebellar neurons derived from human stem cells, including cells from individuals with ASTN2 mutations. Scientists aim to determine whether similar differences exist in human neurons.
Although this study highlights the potential impact of a single gene on autism-like behaviors, autism spectrum disorder arises from a combination of genetic, environmental, and neurobiological factors. Future research will explore how multiple genes interact to influence autism development.
