SPLEEN IMMUNE SYSTEM ALTERATIONS DURING MITRAL CELL DEGENERATION IN PCD MOUSE MODEL

The communication between the immune and central nervous systems may be altered during neurodegeneration. The spleen, a major reservoir of immune cells, plays a key role in filtering blood and modulating systemic lymphocyte activation. In the Purkinje Cell Degeneration (PCD) murine model, which exhibits a dual loss of Purkinje and mitral cells, we have previously characterized an immune response during cerebellar degeneration. Building on this, we aim at investigating the peripheral immune shifts during the gradual degeneration of the olfactory bulb (OB) and exploring the potential modulatory effects of bone marrow transplantation (BMT), which has been shown to improve mitral cell survival. We performed a longitudinal flow cytometric analysis of splenic myeloid and lymphoid populations during OB degeneration, including a cohort subjected to BMT after irradiation.
Initial results indicate that spleen immune cells alterations during OB degeneration are not as numerous as those previously described during cerebellar degeneration. However, we have detected a specific early activation of splenic CD4+ cells at the onset of the neurodegenerative process. On the other hand, preliminary BMT data reveal a systemic shift characterized by a restricted expansion of myeloid compartment in PCD mice compared to WT, alongside a transition toward a more granulocytic profile.
Our findings indicate that PCD neurodegeneration impacts the peripheral immune system in a region-specific and severity-dependent manner. Preliminary data suggest BMT can subtly reshape the systemic immune landscape at the neurodegeneration onset. Understanding of these interactions could offer novel insights into regulating the immune response in these disorders.
Funding: MICINN/JCyL-FEDER/ISCIII