Researchers at Brown University have identified a particular genetic mutation that is associated with certain forms of autism and found a way to reverse its effects in mice. The gene in question is one that produces a protein called NHE6; it is also associated with an autism-like condition called Christianson syndrome, and according to some studies, autism in general. When the NHE6 protein appears in people with autism spectrum disorders, it is downregulated, meaning that it has degraded in some way. This causes problems for synaptic growth and neural communication.

The research team conducted a study in mice—one group with the NHE6 gene mutation and one group without—that involved measuring the acidity in parts of the brain cells of the mice. They found higher levels of acidity in the mice with the mutated gene, which indicated a higher level of degradation in the cell’s receptor protein, called TrkB (a part of the cell that signals the need for synaptic growth). The team observed that increased acidity and lower levels of the TrkB protein were linked to diminished neural branching as well as weaker synapses. In a more acidic environment, the synapses made fewer connections between neurons and the connections that were present were less mature. These results fit with the current body of neurological evidence for autism spectrum disorders being the result of communication difficulties between various sectors of the brain.

Once the researchers had identified the problem—too much acidity due to the genetic mutation—they searched for a solution. They hypothesized that the acidity was caused by the absence of the NHE6 gene and that the acid was causing the TrkB protein to degrade. To test the theory, they treated the mice’s mutant cells with a compound called leupeptin. After the treatment, the TrkB’s signaling levels jumped to levels close to what would be expected from normal cells.

An important finding from this study is that neural growth is not blocked by the MHE6 mutation, but rather it is the resultant processes that cause the signal blockage. There are already pharmaceutical treatments that can overcome the problem of increased acidity, as the researchers did with the mice, but more research is needed to discover whether this is a valid treatment for Christianson syndrome or autism more broadly. However, this does have serious implications for a potential treatment of autism spectrum disorders on a neurological level.

This research is published in the journal Neuron.

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