New Insights into Gene Linked to Rare Brain Disorder and Epilepsy
Researchers have recently uncovered fascinating insights into a gene called SLC35A2, which is linked to a rare condition that affects brain development and can cause epilepsy, known as mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). While SLC35A2 mutations have been flagged as genetic markers for this condition, how this gene influences brain development and contributes to seizure activity has remained a bit of a mystery. A new study aimed to shed light on these questions using specially designed mouse models.
To dig deeper, the scientists created two types of mice where the SLC35A2 gene was selectively turned off in specific brain cell types. One model targeted excitatory neurons and glial cells (the support cells in the brain), while the other focused on oligodendrocytes, which are crucial for the insulation of nerve fibers. As a result, they were able to observe how knocking out SLC35A2 in these different lineages affected brain structure and function.
What they found was quite striking. Mice that had the SLC35A2 gene knocked out in excitatory neurons and glial cells faced severe issues, including premature death, abnormal brain structure, and early seizures. These symptoms closely mirrored those seen in humans with MOGHE. Further experiments showed that the absence of SLC35A2 disrupted the normal process of neuron development, leading to delays in their migration to the areas of the brain where they are needed.
On the flip side, when researchers knocked out SLC35A2 specifically in oligodendrocytes, the mice still showed signs of increased glial cell density and abnormal brain wave patterns, but interestingly, they did not develop seizures. This suggests that the role of SLC35A2 in neurons is particularly crucial when it comes to the development of epilepsy. In summary, this study not only pinpoints SLC35A2 as a key player in brain development and seizure activity but also highlights the importance of neurons in the brain’s response to this genetic variant. It opens up new avenues for understanding and potentially treating MOGHE and related conditions.