Abstract
Batten's disease is the most abundant childhood neurodegenerative disorder, significantly decreasing children's quality of life and preventing important milestones from being reached.
CLN6 Batten disease is caused by a mutation in the CLN6 protein, causing the function of CLN6 to be lost. Symptoms include vision loss, mobility loss, seizures, and intellectual decline. Research for treatments against Batten's disease has been neuron-focused in the past, preventing advancements in successful therapies. Glial cells are now becoming an increasingly appreciated area of research, allowing our understanding of disease progression to become more advanced.
Today, research focused on the potential role of astrocytes and microglia in disease progression is a hot topic that can hopefully advance the understanding of the driver behind neurodegeneration. In the past glial cells were an under-explored target; however, their vital roles in supporting neuronal health and neuroinflammation have led to the hypothesis that glial cells may play more influential roles in disease progression than was once believed.
This research aims to investigate the role astrocytes play in CLN6 Batten disease, determining how the dysfunction of the lysosomal system in astrocytes affects the development of the disease. A mouse model with CLN6 knocked out in astrocytes was used to visualize the presence of CLN6 Batten disease pathologies (CLN6 fl/flAldh). Cell numbers, glial activation and lysosomal function were assessed via immunohistochemistry with different cell markers.
Significant results are limited from the 4-month-old CLN6 fl/flAldh mouse model. When lysosomal intensity was measured in astrocytes, microglia, and neurons, no significant differences were observed between the control and the knock-out mice. No significant differences were seen again when investigating the number of each cell type present.
The area of glial cells was also investigated as the activation of these cells is a common pathology in CLN6 Batten disease, and an increase in size is a known morphology change in activation states. Astrocytes experienced a significant increase in area when comparing the control to the knock-out mice. Results from this study show limited significant results; in future experiments, older mice will be studied and could show more pronounced pathologies.
These results demonstrate how astrocytes lacking CLN6 could potentially cause CLN6 Batten disease and open up a new area of therapeutic targets that may also be applied to other diseases caused by lysosomal dysfunction, however further research is needed over a longer period.