Primary cilia structure is prolonged in enteric neurons of Alzheimerʼs Disease model mice

Introduction Neurodegenerative diseases such as Alzheimerʼs disease (AD) have long been acknowledged as disorders of the central nervous system (CNS). However, this dogma has been challenged in recent years with attention focusing on a more systemic perspective, which includes investigating pathophysiological changes in the gut. This association is intriguing since the gut contains the largest neuronal system outside the CNS – the enteric nervous system (ENS).

Methods The neurodegeneration mouse model 5 xFAD was used to analyze possible changes in gut functionality by organ bath measurement of peristalsis movement. Subsequently, we cultured primary enteric neurons from mutant mice and wild type littermate controls and assessed for cellular pathomechanisms. Neurite mass was quantified within transwell culturing experiments. Using different markers for the primary cilium, cilia number and length were determined using fluorescence microscopy.

Results Although we saw changes in gut motility and neurite mass in mutant mice, we were not able to detect a change in average cilia length or number of ciliated cells. However we did see a larger distribution of longer cilia in cultures generated from mutant mice, possibly suggesting a change in ciliary homeostasis.

Conclusion Our study indicates that although the gut of genetic AD model mice is affected by the disease-driving transgenes, general ciliary structure seems to be preserved in cultivated enteric neurons. Potential changes on the sub-organelle level require further investigations.