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.

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>

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>

혈관성 치매

이영민(Young Min Lee),김어수(Eosu Kim),박제민(Je Min Park) 대한노인정신의학회 2012 노인정신의학 Vol.16 No.2

Vascular dementia (VaD) is a dementia syndrome produced by vascular damage to the brain and increases in incidence with ad-vancing age. Early Identification and diagnosis of VaD is particularly importent since its course may be modifiable through control-ling vascular risk factors. VaD is heterogeneous and consists of several syndromes : multi-infarct dementia, strategic single infarcts dementia, and subcortical vascular dementia. The diagnosis of VaD is based on several features 1) dementia, 2) evidence of cere-brovascular disease, and 3) temporal relationship between dementia and cerebrovascular disease. Treatment of VaD includes control of vascular risk factors, prevention of further vascular injury and treatment of cognitive impairment. Cholinesterase inhibitors pro-vide symptomatic benefits in treatment of VaD.

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>

뇌척수액과 말초혈액 내 알츠하이머병의 생화학적 생체표지자

이영민(Young Min Lee),최원정(Won-Jung Choi),박민선(Minsun Park),김어수(Eosu Kim) 대한노인정신의학회 2012 노인정신의학 Vol.16 No.1

The diagnosis of Alzheimer’s disease (AD) is still obscure even to specialists. To improve the diagnostic accuracy, to find at-risk people as early as possible, to predict the efficacy or adverse reactions of pharmacotherapy on an individual basis, to attain more reliable results of clinical trials by recruiting better defined participants, to prove the disease-modifying ability of new candidate drugs, to establish prognosis-based therapeutic plans, and to do more, is now increasing the need for biomarkers for AD. Among AD-related biochemical markers, cerebrospinal beta-amyloid and tau have been paid the most attention since they are materials directly interfacing the brain interstitium and can be obtained through the lumbar puncture. Level of beta-amyloid is reduced whereas tau is increased in cerebrospinal fluid of AD patients relative to cognitively normal elderly people. Remarkably, such information has been found to help predict AD conversion of mild cognitive impairment. Despite inconsistent findings from previous studies, plasma beta-amyloid is thought to be increased before the disease onset, but show decreasing change as the disease progress. Regarding other peripheral biochemical markers, omics tools are being widely used not only to find useful biomarkers but also to generate novel hypotheses for AD pathogenesis and to lead new personalized future medicine.

Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling

Kang, Somang,Kim, Chul-Hoon,Jung, Hosung,Kim, Eosu,Song, Ho-Taek,Lee, Jong Eun Elsevier 2017 NEUROPHARMACOLOGY - Vol.113 No.1

<P><B>Abstract</B></P> <P>The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from <SMALL>L</SMALL>-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, <I>p</I>-Akt, and <I>p</I>-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal.</P> <P><B>Highlights</B></P> <P> <UL> <LI> HFD induces both peripheral insulin resistance and neuronal insulin resistance. </LI> <LI> HFD evokes Alzheimer's disease like alterations; accumulation of Aβ, p-tau, impairment of cognition. </LI> <LI> AGM rescues HFD induced insulin resistance. </LI> <LI> AGM retrieves blunted brain insulin signalling and reduces Aβ, p-tau. </LI> <LI> AGM improves learning and memory functions in HFD mice. </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.

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.

Age- and Diet Type-Dependent Metabolic Disorder in AD Mouse Model

Do Yup Lee,Soo Jin Park,Yu-Jin Kang,Eosu Kim 한국식품영양과학회 2018 한국식품영양과학회 학술대회발표집 Vol.2018 No.10