1. 제 목 : Role of Arp2/3 in the Pathophysiology of Schizophrenia
2. 연 자 : 김일환 박사
3. 소 속 : Department of Cell Biology, Duke University, Medical School
4. 일 시 : 2013. 05. 16. (목) 오후 2시
5. 장 소 : 고려대 의과대학 제 1의학관 (구관) 4층 4강의실
6. 내 용 :
Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known genetic risk factors for psychiatric disease are related to the regulation of actin polymerization, which plays a key role in synaptic plasticity. To gain insight into and test the possible pathogenetic role of this pathway, we designed a conditional knockout of the Arp2/3 complex, a conserved final output for actin signaling pathways that orchestrates de novo actin polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in forebrain excitatory neurons leads to an asymmetric structural plasticity of dendritic spines that is followed by a progressive, yet profound, loss of spine synapses. Significantly, this progression of synaptic deficits corresponds with an evolution of behavioral symptoms relevant to schizophrenia and normalized by antipsychotics. Together these results point to the dysfunction of actin signaling, specifically that which converges to regulate Arp2/3, as an important cellular pathway that may contribute to the etiology of schizophrenia.
7. 문 의 : 02-2286-1153