Analysis of MHC class I-dependent reactivity of glial cell after nervous system lesions by in vivo two-photon imaging

Abstract

The interaction between motoneurons and glial cells has a crucial role for survival, regulation of functional state and synaptic connectivity in the spinal cord. Understanding the basic functions of glial cells and motoneuron interaction will contribute to the development of new strategies in order to promote regeneration after injury. After lesion, glial cells also undergo a series of morphofunctional changes: astrocytes quickly respond to injury with structural reorganization of their cytoskeloton resulting in changes of their processes that interpose between injured motoneuron membranes and the retracted synaptic terminals and microglia reacts with hyperplasia and hypertrophy after axotomy. Several new studies provide strong evidence that neurons express molecules that, originally, were assumed as immune system-specific. Among them, molecules of the histocompatibility complex class I (MHC I). Recent results indicate that MHC I signaling can be used by neurons and glia to interact both in normal and in pathological processes. Microglial cells express MHC I after lesion while the reactivity of astrocytes is affected by MHC I modulation, thereby changing the synapse plasticity process. In this context, the primary aim is to understand how microglial cells and astrocytes respond to nervous system injuries in an MHC class I-dependent manner. For this purpose we will use combination of transgenic animal models, retrograde tracer injection, 2P-LSM and surgery techniques to be able to image in vivo motoneurons and circumjacent glial cells localized in the ventral horn of spinal lumbar intumescence. (AU)