Cofilin expression induces cofilin-actin rod formation and disrupts synaptic structure and function in Aplysia synapses

摘要

Cofilin-actin rods are inclusion-like structures that are induced by certain chemical or physical stresses in cultured cells, and the rods formed in neurons are thought to be associated with neurodegen-eration. Here, we cloned an Aplysia cofilin homolog and over-expressed it in cultured neurons. Overexpressed cofilin formed rod-like structures that included actin. The overall neuronal morphology was unaffected by cofilin overexpression; however, a decrease in number of synaptic varicosities was observed. Consistent with this structural change by cofilin overexpression, the synaptic strength was reduced, and furthermore, the long-term facilitation elicited by repeated pulses of 5-hydroxytryptamine was impaired in sensory-to-motor synapses. However, cofilin overexpression did not induce programmed cell death. These findings suggest that the formation of cofilin-actin rod-like structures can lead to neurodegeneration, and this might be a mechanism of rundown of neuronal and synaptic function without cell death in neurodegenerative diseases.