ABSTRACT
Epilepsy is a common and severe brain disease affecting >65 million people worldwide. Recent studies have shown that kinesin superfamily motor protein 17 (KIF17) is expressed in neurons and is involved in regulating the dendrite-targeted transport of N-methyl-D-aspartate receptor subtype 2B (NR2B). However, the effect of KIF17 on epileptic seizures remains to be explored. We found that KIF17 was mainly expressed in neurons and that its expression was increased in epileptic brain tissue. In the kainic acid (KA)-induced epilepsy mouse model, KIF17 overexpression increased the severity of epileptic activity, whereas KIF17 knockdown had the opposite effect. In electrophysiological tests, KIF17 regulated excitatory synaptic transmission, potentially due to KIF17-mediated NR2B membrane expression. In addition, this report provides the first demonstration that KIF17 is modified by SUMOylation (SUMO, small ubiquitin-like modifier), which plays a vital role in the stabilization and maintenance of KIF17 in epilepsy.
Subject(s)
Animals , Mice , Epilepsy/metabolism , Kinesins/metabolism , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Seizures/metabolismABSTRACT
Neuronal polarity is involved in multiple developmental stages, including cortical neuron migration, multipolar-to-bipolar transition, axon initiation, apical/basal dendrite differentiation, and spine formation. All of these processes are associated with the cytoskeleton and are regulated by precise timing and by controlling gene expression. The P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) gene for example, is known to be important for cytoskeletal reorganization, cell motility, and migration. Deficiency of P-Rex1 protein leads to abnormal neuronal migration and synaptic plasticity, as well as autism-related behaviors. Nonetheless, the effects of P-Rex1 overexpression on neuronal development and higher brain functions remain unclear. In the present study, we explored the effect of P-Rex1 overexpression on cerebral development and psychosis-related behaviors in mice. In utero electroporation at embryonic day 14.5 was used to assess the influence of P-Rex1 overexpression on cell polarity and migration. Primary neuron culture was used to explore the effects of P-Rex1 overexpression on neuritogenesis and spine morphology. In addition, P-Rex1 overexpression in the medial prefrontal cortex (mPFC) of mice was used to assess psychosis-related behaviors. We found that P-Rex1 overexpression led to aberrant polarity and inhibited the multipolar-to-bipolar transition, leading to abnormal neuronal migration. In addition, P-Rex1 overexpression affected the early development of neurons, manifested as abnormal neurite initiation with cytoskeleton change, reduced the axon length and dendritic complexity, and caused excessive lamellipodia in primary neuronal culture. Moreover, P-Rex1 overexpression decreased the density of spines with increased height, width, and head area in vitro and in vivo. Behavioral tests showed that P-Rex1 overexpression in the mouse mPFC caused anxiety-like behaviors and a sensorimotor gating deficit. The appropriate P-Rex1 level plays a critical role in the developing cerebral cortex and excessive P-Rex1 might be related to psychosis-related behaviors.
ABSTRACT
Objective To evaluate the compliancy of HIV pre-exposure prophylaxis (PREP) in men who have sex with men (MSM) in Chengdu,Sichuan province,and explore the influencing factors.Methods From 1 July 2013 to 30 September 2015,a random,open,multi-center and parallel control intervention study was conducted in 328 MSM enrolled by non-probability sampling in Chengdu.The MSM were divided into 3 groups randomly,i.e.daily group,intermittent group (before and after exposure) and control group.Clinical follow-up and questionnaire survey were carried out every 3 months.Their PrEP compliances were evaluated respectively and multivariate logistic regression analysis was conducted to identify the related factors.Results A total of 141 MSM were surveyed,in whom 59(41.8％) had good PrEP compliancy.The PrEP compliancy rate was 69.0％ in daily group,higher than that in intermittent group (14.3％),the difference had significance (x2=45.29,P＜0.001).Multivariate logistic analysis indicated that type of PrEP was the influencing factors of PrEP compliancy.Compared with daily group,the intermittent group had worse PrEP compliancy (OR=0.07,95％CI:0.03-0.16).Conclusion The PrEP compliance of the MSM in this study was poor,the compliancy would be influenced by the type of PREP.
ABSTRACT
Objective To evaluate the compliancy of HIV pre-exposure prophylaxis (PREP) in men who have sex with men (MSM) in Chengdu,Sichuan province,and explore the influencing factors.Methods From 1 July 2013 to 30 September 2015,a random,open,multi-center and parallel control intervention study was conducted in 328 MSM enrolled by non-probability sampling in Chengdu.The MSM were divided into 3 groups randomly,i.e.daily group,intermittent group (before and after exposure) and control group.Clinical follow-up and questionnaire survey were carried out every 3 months.Their PrEP compliances were evaluated respectively and multivariate logistic regression analysis was conducted to identify the related factors.Results A total of 141 MSM were surveyed,in whom 59(41.8％) had good PrEP compliancy.The PrEP compliancy rate was 69.0％ in daily group,higher than that in intermittent group (14.3％),the difference had significance (x2=45.29,P＜0.001).Multivariate logistic analysis indicated that type of PrEP was the influencing factors of PrEP compliancy.Compared with daily group,the intermittent group had worse PrEP compliancy (OR=0.07,95％CI:0.03-0.16).Conclusion The PrEP compliance of the MSM in this study was poor,the compliancy would be influenced by the type of PREP.