活性酸素シグナルの小脳機能への作用と生理的老化

抄録

Aging is associated with decline in various brain functions, having a significant impact on individual's quality of life. Synaptic plasticity is cellular basis for higher brain functions, including learning and memory and cognition. Although there are various reports on the age-dependent decline in higher brain functions, profile and molecular mechanism of age-dependent changes in cerebellar synaptic plasticity are not fully understood.

Cerebellar synapses of mouse are excellent models for the studies on age-dependent changes in synaptic plasticity, because the cerebellar neuronal circuit is simple and various types of synaptic plasticity, including long-term depression (LTD) and long-term potentiation (LTP) at parallel fiber (PF)-to-Purkinje cell (PC) synapse (PF synapse), are identified. However, profile and molecular mechanism of age-dependent changes in cerebellar synaptic plasticity have yet to be examined.

In this symposium, I will introduce our recent studies indicating that involvements of ROS-related signaling in inhibition of LTP at PF synapse (PF-LTP) in the aged cerebellum. ROS impairs PF-LTP and nitric oxide-induced Ca²⁺ release, which is essential for the induction of PF-LTP, through the inhibition of S-nitrosylation of intracellular Ca²⁺ release channel. Surprisingly, ROS is also indicated to be involved in cerebellar-dependent motor learning as well as PF-LTD in young-adult cerebellum. Taken together, these observations suggest dual functions of ROS in physiological and pathophysiological events in brain systems in young and aged mouse, respectively.