Summary: Researchers have discovered crucial insights into how autism spectrum disorders (ASDs) can develop at early stages of brain formation. Using mouse models, the team found that environmental factors that cause autism-like symptoms are linked to early changes in neurotransmitter activity in the brain.
Specifically, they observed that a temporary switch from the inhibitory neurotransmitter GABA to the excitatory neurotransmitter glutamate in neonatal mice could lead to the development of ASD-like behaviors, such as repetitive actions and reduced social interaction, later in life. By intervening at this early stage and reversing the neurotransmitter switch, the researchers were able to prevent these behaviors from developing in adulthood.
Key facts
- Early changes in neurotransmitters in the brain’s prefrontal cortex can trigger ASD.
- Intervention during early brain development prevented autistic-like behaviors in mice.
- Study offers new avenues for early intervention in autism spectrum disorders.
Source: University of California San Diego
Autism spectrum disorders (ASD) involve mild to severe impairment in social, behavioral, and communication skills. These disorders can have significant impacts on performance in school, work, and other areas of life.
However, researchers lack knowledge about how these disorders appear in the early stages of development.
Neurobiologists at the University of California, San Diego, have found evidence of altered nervous system development in mouse models of autism spectrum disorder.
They linked environmentally induced forms of ASD to changes in neurotransmitters, the chemical messengers that allow neurons to communicate with each other.
They also found that manipulating these neurotransmitters early in development can prevent the onset of autistic-like behaviors.
The study is published on August 23, 2024 in the Proceedings of the National Academy of Sciences.
“In looking for the root causes of autism spectrum disorder behaviors in the brain, we discovered an early change in neurotransmitters that is a good candidate for the root cause,” said Professor Nicholas Spitzer of the School of Biological Sciences in the Department of Neurobiology and the Kavli Institute for Brain and Mind.
“Controlling the first events that trigger ASD could allow us to develop new forms of intervention to prevent the onset of these behaviors.”
ASD diagnoses have increased in recent years, but how these disorders manifest at critical cellular and molecular levels is not well understood.
The study’s lead author, Swetha Godavarthi, an associate project scientist, and her colleagues studied neurotransmitter expression in the medial prefrontal cortex, an area of the brain often affected in people diagnosed with ASD.
They tested the hypothesis that changes in the type of neurotransmitter expressed by neurons in the prefrontal cortex might be responsible for a chemical imbalance that causes ASD-like behaviors.
Previous studies have shown an increased incidence of ASD in children when pregnant women had an increased immune response or were exposed to certain medications during the first trimester (environmental forms of ASD).
Researchers reproduced ASD in mice by administering to mice in utero with these environmental agents. These agents caused brief loss of the inhibitory neurotransmitter “GABA” and gain of the excitatory neurotransmitter “glutamate” in neonatal mice.
Although this GABA-glutamate transmitter switch reversed spontaneously after a few weeks, adult mice exhibited impaired repetitive grooming behaviors and decreased social interaction.
Bypassing this brief early transmitter switch in neonatal mice prevented the development of these autistic-like behaviors in adults.
“Expression of GABA in neurons that have replaced GABA with glutamate prevents the occurrence of stereotyped repetitive behaviors and reduced social interaction,” Spitzer said.
“These results demonstrate that altered electrical activity and inappropriate excitation of neurons at early stages of development can alter the assembly of the nervous system.”
Alterations in neurotransmitter expression early in development have implications for other behavioral problems later in life, since the rest of the nervous system is then built on a platform of faulty wiring, similar to a house built on an unstable foundation.
“Switching neurotransmitters can alter the assembly of the nervous system and have profound downstream impacts,” Spitzer said.
The researchers say the new findings are consistent with other evidence that altered signaling in the nervous system during early development can lead to negative consequences as the brain matures.
About this news on autism research and brain development
Author: Mario Aguilera
Source: University of California San Diego
Contact: Mario Aguilera – UCSD
Picture: Image credited to Neuroscience News
Original research: The results will appear in PNAS
