Clarification on the role of semaphorin signal transduction mechanism regulating microglial function in brain homeostasis

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Plexin-A1 is a receptor of semaphorins originally found as repulsive axon guidance molecules. Plexin-A1 deficient mice over 14-week-old were revealed to have significant deficits in prepulse inhibition of auditory startle reflex which can be also observed in psychiatric disease such as schizophrenia. Plexin-A1 deficient mice also displayed significant increase in locomotion activity and grooming behavior and age-dependent microglial overactivation and demyelination. Thus, plexin-A1 deficient mice is an animal model useful to obtain a novel finding which helps us clarify the pathogenic mechanism of psychiatric diseases recently suggested to be related to abnormal microglia, but still concealing essentially unknown factors.