Autism-like behavior caused by deletion of vaccinia-related kinase 3 i…
Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation..pdf - 담당교수Kyong Tai Kim
- 조회666
- 작성자최고관리자
- 2017-09-28
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Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell
signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of
VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient
mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social
interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization
were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA
receptor–mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B
(TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and
function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical
role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD.
signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of
VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient
mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social
interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization
were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA
receptor–mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B
(TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and
function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical
role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD.
