Regulation of dendritic spine morphology by Tenm3 at perforant pathway synapses
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Abstract
Alzheimer’s Disease (AD) is a neurodegenerative disease clinically characterized by cognitive decline and pathologically by the accumulation in amyloid β (Aβ) and hyperphosphorylated tau proteins in neurons. During the first stages of the disease tau accumulates specifically in neurons from layer II of Entorhinal Cortex (ECII). By searching for AD-associated variants in genes enriched in these neurons, the lab found evidence supporting the notion that the TENM3 gene contributes to ECII vulnerability. The mechanism by why TENM3 mediates vulnerability is unknown, but previous research from the lab suggests that processes remodeling axonal structure might underlie vulnerability of ECII neurons. In this thesis, we therefore studied the effect of Tenm3 deletion on synapse density and structure in the terminal zone of ECII neurons using a combination of immunofluorescence and electron microscopy. While we did not find any difference in the number of synapses in Tenm3 knockout mice, we found structural differences in their synapses in the outer molecular layer of the dentate gyrus. We found differences in the correlation between pre- and postsynaptic volumes suggesting that Tenm3 participates in the proper adjustment of both sides of the synapse. These findings suggest the possibility that Tenm3 deletions affect communication of the pre- and postsynaptic sides of the synapse.
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2024