Manabu Makinodan: “Social experience-dependent glia development and its association with autism spectrum disorder”
CiNet 1F Conference Room
Department of Psychiatry
Nara Medical University
Multiple lines of evidence have shown that social experience during a juvenile period substantially affects brain function and behaviors in rodents, dogs, and humans. Interestingly, juvenile social experience changes not only brain function, but also brain structure, such as myelination, in mice and humans. In addition, juvenile social experience alters the microglial state in brains of mice. Since recent studies have shown that environmental factors are more contributory to the development of autism spectrum disorder (ASD) than considered in the past, we believe that studies regarding the effects of social experience on the function and structure of mPFC become more valuable in dissecting ASD symptoms in which mPFC is largely impaired.
We found that juvenile social isolation (P21-P35) leads to hypomyelination in the mPFC and microglial activation with an increase of interleukin-6 (IL-6) even after re-socialization with three socially- isolated mice (P36-P65). Since neuron-oligodendrocyte co-culture studies indicated that IL-6 strongly interferes with myelination, the high level of microglia-derived IL-6 expression might be associated with hypomyelination in the mPFC and its relevant abnormal behaviors. In order to prevent an increase of IL-6 in the mPFC, we arranged and compared the intensity of re-socialization by the following means; a socially-isolated mouse with three socially-isolated mice, and a socially-isolated mouse with three socially-reared mice. Surprisingly, re-socialization by three socially-housed mice prevented an increase of IL-6 expression and restored hypomyelination and impaired functions of mPFC. Electronphysiological experiments also revealed that the intensity of re-socialization alters excitatory postsynaptic current into pyramidal cells in the layer V of mPFC.
In this seminar, I will show the implication of social experience- dependent glia development in the mPFC for the pathobiology of ASD and provide the possibility of social intervention for patients with ASD.