Identifying the Biological Basis of Autism
The biological basis of autism — a developmental disorder that poses challenges to an individual’s ability to communicate and interact — has long been disputed amongst medical professionals. This misunderstanding was particularly sensationalized following the release of Dr. Andrew Wakefield’s since-retracted 1998 paper, which concluded that childhood vaccinations, such as the measles, mumps, and rubella (MMR) vaccine, could lead to autism. However, researchers have recently made a breakthrough in the quest for finding the cause of autism, finding that cells called astrocytes play a key role in autism spectrum disorder (ASD) development through abnormal calcium signaling in the brain.
Astrocytes are a key cell type in the brain, as they regulate neurons and the connections between them through processes like the formation of synapses and neuronal-plasticity. Though previous research had shown that ASD individuals had astrocyte abnormalities in postmortem examinations, it was unknown whether the cells are inherently different, or if they become abnormal as a result of autism. To look into this knowledge gap, researchers first derived astrocytes from individuals with ASD and turned them into induced pluripotent stem cells (iPSCs), which are stem cells that can give rise to any type of cell in the body. They then implanted them in the brains of healthy, neurotypical mice. As a result, these mice exhibited repetitive behavior and memory deficits, which are indicative of a reduction in neuronal activity. They also found that the implantation of ASD astrocytes in the neurotypical brain actually disturbed the structure and function of neurons in the hippocampus, the brain region responsible for learning and memory.
Astrocytes are a key cell type in the brain, as they regulate neurons and the connections between them through processes like the formation of synapses and neuronal-plasticity. Though previous research had shown that ASD individuals had astrocyte abnormalities in postmortem examinations, it was unknown whether the cells are inherently different, or if they become abnormal as a result of autism. To look into this knowledge gap, researchers first derived astrocytes from individuals with ASD and turned them into induced pluripotent stem cells (iPSCs), which are stem cells that can give rise to any type of cell in the body. They then implanted them in the brains of healthy, neurotypical mice. As a result, these mice exhibited repetitive behavior and memory deficits, which are indicative of a reduction in neuronal activity. They also found that the implantation of ASD astrocytes in the neurotypical brain actually disturbed the structure and function of neurons in the hippocampus, the brain region responsible for learning and memory.
The researchers also found that the inherent defects in astrocytes derived from individuals with ASD were related to altered calcium signaling. Astrocytes require specific levels of calcium in order to properly interact with neurons; through calcium signaling, the cells can communicate with neurons and regulate the neuronal network. Individuals with ASD had previously been found to have altered calcium signaling in their astrocytes, leading to an unusually high concentration. To test whether the unusually high levels of calcium in the ASD astrocytes were responsible for the observed neuronal and behavioral issues, researchers infected astrocytes from individuals with ASD with a virus that reduced calcium signaling down to levels that were considered normal. Upon implantation of these astrocytes in healthy mice, the mice displayed no cognitive or behavioral issues. The researchers therefore concluded that the altered calcium signaling in ASD astrocytes was the reason for changes in the neuronal network and behavior.
The two main indicators of autism are repetitive behaviors and social deficits; though researchers have uncovered what causes repetitive behaviors, they have yet to figure out what causes social impairment in autism. Regardless, this research has proven to be promising and is essential in working towards demystifying the basis of autism and better informing the general public. Based on this research, treatment for autism in the future could involve limiting calcium fluctuations within astrocytes. This also has major implications for treating other neuropsychiatric disorders like schizophrenia, which is a disease that has similarly been linked to altered cell signaling.
The two main indicators of autism are repetitive behaviors and social deficits; though researchers have uncovered what causes repetitive behaviors, they have yet to figure out what causes social impairment in autism. Regardless, this research has proven to be promising and is essential in working towards demystifying the basis of autism and better informing the general public. Based on this research, treatment for autism in the future could involve limiting calcium fluctuations within astrocytes. This also has major implications for treating other neuropsychiatric disorders like schizophrenia, which is a disease that has similarly been linked to altered cell signaling.
Featured Image Source: Polina Kovalena
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