Targeted Downregulation of kdm4a Ameliorates Tau-engendered Defects in Drosophila melanogaster

BACKGROUND: Tauopathies, a class of neurodegenerative diseases that includes Alzheimer's disease (AD), are characterized by the deposition of neurofibrillary tangles composed of hyperphosphorylated tau protein in the human brain. As abnormal alterations in histone acetylation and methylation show a cause and effect relationship with AD, we investigated the role of several Jumonji domain-containing histone demethylase (JHDM) genes, which have yet to be studied in AD pathology. METHODS: To examine alterations of several JHDM genes in AD pathology, we performed bioinformatics analyses of JHDM gene expression profiles in brain tissue samples from deceased AD patients. Furthermore, to investigate the possible relationship between alterations in JHDM gene expression profiles and AD pathology in vivo, we examined whether tissue-specific downregulation of JHDM Drosophila homologs (kdm) can affect tauR406W-induced neurotoxicity using transgenic flies containing the UAS-Gal4 binary system. RESULTS: The expression levels of JHDM1A, JHDM2A/2B, and JHDM3A/3B were significantly higher in postmortem brain tissue from patients with AD than from non-demented controls, whereas JHDM1B mRNA levels were downregulated in the brains of patients with AD. Using transgenic flies, we revealed that knockdown of kdm2 (homolog to human JHDM1), kdm3 (homolog to human JHDM2), kdm4a (homolog to human JHDM3A), or kdm4b (homolog to human JHDM3B) genes in the eye ameliorated the tauR406W-engendered defects, resulting in less severe phenotypes. However, kdm4a knockdown in the central nervous system uniquely ameliorated tauR406W-induced locomotion defects by restoring heterochromatin. CONCLUSION: Our results suggest that downregulation of kdm4a expression may be a potential therapeutic target in AD.

Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

OBJECTIVE: The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC). METHODS: Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC. RESULTS: When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation. CONCLUSION: These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion.

Abnormal Brain Activity in Social Reward Learning in Children with Autism Spectrum Disorder: An fMRI Study

PURPOSE: We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). MATERIALS AND METHODS: 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. RESULTS: ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyrus. CONCLUSION: These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs.

Changes of transverse mandibular width after intraoral vertical ramus osteotomy

PURPOSE: In order to clarify the correlation of mandibular setback using bilateral intraoral vertical ramus osteotomy (BIVRO) and post-surgical transverse mandibular width (TMW), this study examined the pre- and postsurgical changes in hard and soft tissues of TMW and the relationship of TMW and the amount of mandibular setback. PATIENTS AND METHODS: One-hundred seven patients who had undergone BIVRO were evaluated radiographically and clinically. A comparison study of the changes in hard and soft tissue after surgery in all 107 patients was performed with preoperative, 1 month, 3 month, 6 month and 1 year postoperative posteroanterio cephalograms and clinical photographs by tracing. And this changes were evaluated in parts to amounts of mandibular setback. RESULTS: Statistically significant increases of TMW in hard and soft tissue from preoperative to postoperative 1 month were seen. TMW in hard tissue from 1 month to 1 year postopertive were gradually decreased. TMW in soft tissue was not changed uniformly but almost equal to pre-operative width. And there was no significant correlation between TMW and amount of mandibular setback. CONCLUSIONS: The results show that mandibular setback using BIVRO did not significantly influence increasing of TMW in soft tissue.