Nonverbal Social Behaviors of Patients With Bipolar Mania During Interactions With Virtual Humans

Kim, Eosu,Ku, Jeonghun,Kim, Jae-Jin,Lee, Hyeongrae,Han, Kiwan,Kim, Sun I.,Cho, Hyun-Sang Lippincott Williams Wilkins, Inc. 2009 The Journal of nervous and mental disease Vol.197 No.6

It has been proposed that positive emotional biases could make bipolar manic (BM) patients maintain abnormally approaching behaviors during social interactions. To test this hypothesis, we measured interpersonal distance (IPD) and gaze angle of BM patients and normal controls (NCs) during social interaction in immersive virtual environment. Overall, IPDs of BM patients (n = 20) were greater than those of normal controls (n = 20). The IPD difference was even greater between NCs and BM patients with psychotic features (n = 11) than those without psychotic features (n = 9). Regardless of the presence of psychotic features, BM patients averted their gazes more than NCs, and even more while speaking than while listening. Our results might suggest negativistic social cognition of bipolar patients, as was previously found even during a manic phase, or the role of paranoid symptoms in avoidant social behaviors, in agreement with prior studies with schizophrenic patients. Use of proper space and gaze might have psychotherapeutic implication in developing secure, two-person relationship with bipolar patients regardless of the presence of disrupting manic symptoms.

Mammillothalamic functional connectivity and memory function in Wernicke's encephalopathy

Kim, Eosu,Ku, Jeonghun,Namkoong, Kee,Lee, Wonho,Lee, Kang Soo,Park, Ji-Yeon,Lee, Su Young,Kim, Jae-Jin,Kim, Sun I.,Jung, Young-Chul Oxford University Press 2009 Brain Vol.132 No.2

<P>There is still debate over the neural mechanisms underlying pathogenic and even recovery processes of Wernicke's encephalopathy. Therefore, we attempted to validate the usefulness of resting-state functional connectivity analysis in assessing memory function and its neural correlation with the mammillothalamic tract in patients recovering from Wernicke's encephalopathy. Seven chronic alcoholics recovering from Wernicke's encephalopathy, 14 alcoholic comparisons without Wernicke's encephalopathy, and 14 healthy comparisons underwent functional connectivity MRI scans, as well as verbal and non-verbal memory tests after at least a 1 month abstinence from alcohol. Resting-state functional connectivity strength between the anterior thalamus and the mammillary bodies was investigated by calculating temporal correlations in magnetic resonance signal levels between the two regions during a 5-min passive viewing task. The mean values of the functional connectivity strength between the left anterior thalamus and the ipsilateral mammillary body differed significantly between Wernicke's encephalopathy patients and healthy comparisons (P = 0.014). This connectivity strength in alcoholic comparisons fell between those of the former two groups, with a significant difference from that of healthy comparisons (P = 0.038). In addition, the strength of this left-sided functional connectivity significantly correlated with delayed verbal recall scores (r = 0.771, P = 0.042) and verbal recognition score (r = 0.825, P = 0.022) in patients with Wernicke's encephalopathy. Our findings indicate that memory function in patients recovering from Wernicke's encephalopathy parallels the level of the mammillothalamic functional connectivity; this supports the usefulness of resting-state functional connectivity analysis as a practical alternative to pathological examination of the mammillothalamic tract in living patients with Wernicke's encephalopathy.</P>

알츠하이머병에서 혈장 크레아틴과 염증반응, 인지기능과의 연관성

김민애(Minae Kim),오대종(Dae Jong Oh),김현정(Hyunjeong Kim),조소연(So Yeon Cho),하정희(Junghee Ha),이준영(Jun-Young Lee),김어수(Eosu Kim),김근유(Keun You Kim) 대한노인정신의학회 2021 노인정신의학 Vol.25 No.2

Objective: Creatine, energy buffer in high energy demanding systems including muscle and brain, may play a beneficial role against neuroinflammation in Alzheimer’s disease (AD), and thus be a potential biomarker. This study aimed to compare the levels of plasma creatine between persons with and without AD and investigate associations of plasma creatine levels with cognitive function and blood-based inflammatory markers. Methods: We classified elderly participants by cognitive statuses: normal cognition (NC, n=17), mild cognitive impairment (MCI, n=21), and AD (n=21). To assess cognitive function and inflammatory condition, we performed neuropsychological tests and measured plasma C-reactive protein (CRP) levels, respectively. Results: Plasma creatine levels were comparable among participants with AD, MCI, and NC. In overall participants, plasma creatine levels were not associated with neuropsychological test scores, but negatively associated with plasma CRP levels. In AD group, plasma creatine levels were negatively associated with neuropsychological test scores and, although not significant, CRP levels (p=0.086). In participants without AD (NC plus MCI), these associations disappeared. Conclusion: Plasma creatine levels may not be useful as a biomarker indicating cognitive statuses. However, our results suggest that, in AD, plasma levels of creatine might reflect the extent of neuroinflammation as well as cognitive deterioration.

Cholinesterase Inhibitor Donepezil Increases Mitochondrial Biogenesis through AMP-Activated Protein Kinase in the Hippocampus

Kim, Eosu,Park, Minsun,Jeong, Jihyeon,Kim, Hyunjeong,Lee, Su Kyoung,Lee, Eun,Oh, Byoung Hoon,Namkoong, Kee S. Karger 2016 Neuropsychobiology Vol.73 No.2

<P>Objective: Donepezil, a widely prescribed drug for Alzheimer's disease (AD), is now considered to have multimodal actions beyond cholinesterase inhibition. We aimed to see whether donepezil enhances mitochondrial biogenesis and relevant signaling pathways since mitochondrial dysfunction is a key feature of the hypometabolic AD brain. Methods: As a metabolic gauge, AMP-activated protein kinase (AMPK) was investigated as a tentative mediator of neurometabolic action of donepezil. Changes in phospho-AMPK levels, mitochondrial biogenesis, and ATP levels were measured upon donepezil treatment using neuroblastoma cells, primary cultured neurons and ex vivo hippocampal tissue of adult mice. Results: Donepezil dose-dependently increased mitochondrial biogenesis and ATP levels as well as expression of PGC-1 alpha and NRF-1 in neuroblastoma cells. Donepezil dose-dependently activated AMPK; however, inhibition of AMPK abolished the observed effects of donepezil, indicating that AMPK is a key mediator of donepezil's action. Notably, mitochondrial biogenesis upon donepezil treatment was mainly observed within dendritic regions of primary cultured hippocampal neurons. Levels of synaptic markers were also increased by donepezil. Finally, AMPK-dependent mitochondrial biogenesis by donepezil was confirmed in organotypic hippocampal tissue. Conclusions: Our findings indicate that AMPK/PGC-1 alpha signaling is involved in beneficial actions of donepezil on neurometabolism. Pharmacological activation of AMPK might be a promising approach to counteract AD pathogenesis associated with brain hypometabolism. (C) 2016 S. Karger AG, Basel</P>

Lipidomic alterations in lipoproteins of patients with mild cognitive impairment and Alzheimer’s disease by asymmetrical flow field-flow fractionation and nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry

Kim, San Ha,Yang, Joon Seon,Lee, Jong Cheol,Lee, Ji-Yeon,Lee, Jun-Young,Kim, Eosu,Moon, Myeong Hee Elsevier 2018 Journal of chromatography Vol.1568 No.-

<P><B>Abstract</B></P> <P>Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with the clinical symptom of the progressive loss of cognitive function and mild cognitive impairment (MCI) is a translational state between cognitive changes of normal aging and AD. Lipid metabolism and pathogenesis of Alzheimer’s disease (AD) are closely linked. Despite obviously discrete lipidome constitutions across lipoproteins, lipidomic approaches of AD has been mostly conducted without considering lipoprotein-dependent alterations. This study introduces a combination of asymmetrical flow field-flow fractionation (AF4) and nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry (nUHPLC-ESI-MS/MS) for a comprehensive lipid profiling in different lipoprotein level of patients plasma with AD and amnestic MCI in comparison to age-matched healthy controls. Lipoproteins in plasma samples were size-sorted by a semi-preparative scale AF4, followed by non-targeted lipid identification and high speed targeted quantitation with nUHPLC-ESI-MS/MS. It shows 14 significantly altered high abundance lipids in AD, exhibiting >2-fold increases (<I>p </I>< 0.01) in LDL/VLDL including triacylglycerol, ceramide, phosphatidylethanolamine, and diacylglycerol. Three lipid species (triacylglycerol 50:1, diacylglycerol 18:1_18:1, and phosphatidylethanolamine 36:2) showing a strong correlation with the degree of brain atrophy were found as candidate species which can be utilized to differentiate the early stage of MCI when simple Mini-Mental State Examination results were statistically incorporated. The present study elucidated lipoprotein-dependent alterations of lipids in progression of MCI and further to AD which can be utilized for the future development of lipid biomarkers to enhance the predictability of disease progress.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Lipoprotein-dependent lipidomic analysis of Alzheimer’s disease. </LI> <LI> Size-sorting of lipoproteins by Flow FFF and lipid analysis by nUHPLC-MS/MS. </LI> <LI> Fourteen high-abundance lipids showed significant changes in Alzheimer’s disease. </LI> <LI> Three lipids in LDL/VLDL were specific to mild cognitive impairment. </LI> </UL> </P>

Emotional Priming With Facial Exposures in Euthymic Patients With Bipolar Disorder

Su Kim, Taek,Young Lee, Su,Yeon Ha, Ra,Kim, Eosu,Kyoon, Suk,Ha, Kyooseob,Cho, Hyun-Sang Lippincott Williams Wilkins, Inc. 2011 The Journal of nervous and mental disease Vol.199 No.12

ABSTRACT: People with bipolar disorder have abnormal emotional processing. We investigated the automatic and controlled emotional processing via a priming paradigm with subliminal and supraliminal facial exposure. We compared 20 euthymic bipolar patients and 20 healthy subjects on their performance in subliminal and supraliminal tasks. Priming tasks consisted of three different primes according to facial emotions (happy, sad, and neutral) followed by a neutral face as a target stimulus. The prime stimuli were presented subliminally (17 msec) or supraliminally (1000 msec). In subliminal tasks, both patients and controls judged the neutral target face as significantly more unpleasant (negative judgment shift) when presented with negative emotion primes compared with positive primes. In supraliminal tasks, bipolar subjects showed significant negative judgment shift, whereas healthy subjects did not. There was a significant group × emotion interaction for the judgment rate in supraliminal tasks. Our finding of persistent affective priming even at conscious awareness may suggest that bipolar patients have impaired cognitive control on emotional processing rather than automatically spreading activation of emotion.

Particulate matter increases beta-amyloid and activated glial cells in hippocampal tissues of transgenic Alzheimer's mouse: Involvement of PARP-1

Jang, Sooah,Kim, Eun Woo,Zhang, Yinhua,Lee, Jimin,Cho, So Yeon,Ha, Junghee,Kim, Hyunjeong,Kim, Eosu Elsevier 2018 Biochemical and biophysical research communication Vol.500 No.2

<P><B>Abstract</B></P> <P>Exposure to air pollutants, such as particulate matter (PM), has been implicated in neurodegenerative disorders including Alzheimer's disease (AD). However, direct effects of PM on production of β-amyloid (Aβ), a key pathogenic molecule in AD, and its underlying mechanism are still elusive. Given PM's potential to induce oxidative stress in other tissues, we hypothesized that poly(ADP-ribose) polymerase (PARP-1) might be involved in PM-induced neurotoxicity. To address this, we used an <I>ex vivo</I> model of AD, the organotypic hippocampal slice tissue culture from old (12-14 months-of-age) triple transgenic 3xTg-AD mice. First, we observed that fine PM (aerodynamic diameter < 4 μm) can dose-dependently activate PARP-1 and decrease NAD<SUP>+</SUP> levels in Neuro2A cells. PARP-1 activation did occur under concentrations of PM which did not affect cell viability. Next, we observed that direct treatment of PM increased Aβ levels and activated glial cells in the <I>ex vivo</I> hippocampal tissues of 3xTg-AD mice. PM-induced glial activation was most prominent in CA1 region of the hippocampal tissue. Notably, we found that pharmacological inhibition of PARP-1 reversed both PM-induced Aβ increase and glial activation, arguing the possible involvement of PARP-1 in PM-induced AD pathogenesis. Our findings suggest that PARP-1 might be a potential molecular target, responsible for mediating negative effects of PM on the brain. Modulating PARP-1 activity could be a promising approach to prevent or alleviate PM-related environmental neurotoxicity which could initiate AD pathogenesis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Particulate matter (PM) activates PARP-1 in neuronal cells. </LI> <LI> PM increases beta-amyloid in <I>ex vivo</I> hippocampus of 3xTg-AD mouse. </LI> <LI> PM activates glial cells in <I>ex vivo</I> hippocampus of 3xTg-AD mouse. </LI> <LI> Pharmacological inhibition of PARP-1 reverses PM-induced AD pathologies. </LI> <LI> PARP-1 inhibition would be a promising approach counteracting PM's neurotoxicity. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Long-Term Culture of Organotypic Hippocampal Slice from Old 3xTg-AD Mouse: An ex vivo Model of Alzheimer’s Disease

Sooah Jang,Hyunjeong Kim,Hyejin Kim,SuKyoung Lee,EunWoo Kim,KeeNam koong,Eosu Kim 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.2

Objective-Conventional methods for organotypic hippocampal tissue slice culture (OHSC) have shown several disadvantages or limitations regarding age of animals used, duration of culture and difficulty using neurodegenerative models. Therefore, we tried to establish OHSC from old 3xTg-Alzheimer’s disease (AD) mice for longer period (over 4 weeks) and to validate utility of this system as a valid platform for translational neuroscience of AD. Methods-OHSC was performed with old 3xTg-AD mice (12-14 months), old wild type mice (12-14 months) and young 3xTg-AD mice (2-4 months) using serum-free medium for 4 weeks. Hippocampal structure was evaluated by 4’, 6-diamidino-2-phenylindole (DAPI) intensity and neuronal metabolism was measured by Alamarblue assay. Pathologic characteristics of AD were also investigated; β-amyloid levels by ELISA, amyloid plaque deposition by Thioflavin-S staining, and glial activation by immunohistochemistry. Results-Following 4-week culture in serum-free media, hippocampal cells and layers were well preserved in cultured slices from old AD mice as was in those from young AD and old wild type mice. On the contrary, excessive regression of total visible cells was observed in conventional serum-containing medium regardless of genotype of mice. In parallel with this well preserved structure, major pathologic characteristics of AD were also well manifested in hippocampal slices from old AD mice. Conclusion-Our findings suggest that long-term OHSC from old 3xTg-AD mouse can serve as a promising ex vivo system for studies on pathophysiology of AD, especially with the minimum number of sacrifice of experimental animals.

Deficits in Eye Gaze During Negative Social Interactions in Patients With Schizophrenia

Choi, Soo-Hee,Ku, Jeonghun,Han, Kiwan,Kim, Eosu,Kim, Sun I.,Park, Junyoung,Kim, Jae-Jin Lippincott Williams Wilkins, Inc. 2010 The Journal of nervous and mental disease Vol.198 No.11

Impaired social functioning has been reported in patients with schizophrenia. This study aimed to examine characteristics of interpersonal behaviors in patients with schizophrenia during various social interactions using the virtual reality system. Twenty-six patients and 26 controls engaged in the virtual conversation tasks, including 3 positive and 3 negative emotion-laden conversations. Eye gaze and other behavioral parameters were recorded during the listening and answering phases. The amount of eye gaze was assessed as smaller in the patients than in the controls. A significant interaction effect of group status and emotional type was found for the listening phase. The amount of eye gaze in the patients inversely correlated with self-rated scores of assertiveness for the listening phase. These results suggest that the patients displayed inadequate levels of augmentations in eye gaze during negative emotional situations. These deficits should be considered in the treatment and social skills training for patients with schizophrenia.

Suppression of AIMP1 protects cognition in Alzheimer’s disease model mice 3xTg-AD

Jang, Sooah,Lee, Jung Ho,Sohn, Bo Kyung,Kim, Eosu,Park, Sang Gyu,Yoon, Kang Jun,Park, Minsun,Kim, Eun Woo,Jeong, Jihyeon,Lee, Jun-Young,Kim, Chul Hoon,Namkoong, Kee Wolters Kluwer Health | Lippincott Williams Wilkin 2017 NEUROREPORT - Vol.28 No.2

<P>Neuroinflammation has been raised as a candidate of unifying pathogenesis and a target of a disease-modifying strategy for Alzheimer's disease (AD). Aminoacyl-tRNA synthetase complex (ARS)-interacting multifunctional protein 1 (AIMP1) is a cytokine that is known to amplify the actions of tumor necrosis factor-a and to be involved in microglial activation and neuronal death. In this respect, AIMP1 could be a plausible target for the treatment of AD. Therefore, we aimed to examine whether anti-AIMP1 antibody could exert therapeutic effects against cognitive impairment using 3xTg-AD mice. Through the passive avoidance test, we found that an intraperitoneal injection of anti-AIMP1 antibody over 4 weeks was effective in protecting memory function in 3xTg-AD mice (16 weeks old). In addition, to address the translational implications of AIMP1, we measured blood AIMP1 levels in patients with AD (n=22), mild cognitive impairment (n=25), and normal cognition (n=23). Blood AIMP1 levels were associated negatively with global cognitive function and were significantly higher in individuals with a higher degree of medial temporal lobe atrophy, which is one of the representative clinical markers of AD. Our results suggested a possible association of AIMP1 with AD pathogenesis, as well as the potential of the anti-AIMP1 antibody as a novel therapeutic option for AD. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.</P>