Session Title: Neurodevelopment and Neurodegeneration
ULTRASTRUCTURAL ANALYSIS OF SYNAPTIC LOSS IN MURINE PRION DISEASE: EVIDENCE FOR PHAGOCYTOSIS BY PYRAMIDAL CELL DENDRITIC SPINES
Z. Siskova, V. O'Connor, V.H. Perry
Dysfunction and loss of synapses precede neuronal death in various neurodegenerative diseases. We have observed that initial changes of ultrastructure of synaptic compartments mediate progressive loss of glutamatergic synapses in the stratum radiatum of the hippocampus from early stages of prion pathology in ME7 mouse model. We detected significant decrease in the density and size of Type I synapses from early stage of the disease. Profound changes in PSD geometry facilitated subsequent invagination and removal of asymmetric synaptic boutons by dendritic spines of postsynaptic CA1 pyramidal neurons. Concomitantly with a decrease of Type I synaptic density, compensatory mechanism manifested by an increase of size of remaining synapses was observed at latter stages. These findings support a model of phagocytosis- like process during chronic neurodegeneration that allow a removal of degenerating synapse by means of its PSD-mediated internalization by dendritic spine. These events have their analogy in postnatal control of synaptic distribution and density reported to occur during the development of spinal motoneuronal circuit in a newborn cat (Ronnevi, 1979).