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Asymmetry of Dopamine D2/3 Receptor Availability in Dorsal Putamen and Body Mass Index in Non-obese Healthy Males.

Sang Soo CHO ; Eun Jin YOON ; Sang Eun KIM

Experimental Neurobiology.2015;24(1):90-94. doi:10.5607/en.2015.24.1.90

The dopaminergic system is involved in the regulation of food intake, which is crucial for the maintenance of body weight. We examined the relationship between striatal dopamine (DA) D2/3 receptor availability and body mass index (BMI) in 25 non-obese healthy male subjects using [11C]raclopride and positron emission tomography. None of [11C]raclopride binding potential (BP) values (measures of DA D2/3 receptor availability) in striatal subregions (dorsal caudate, dorsal putamen, and ventral striatum) in the left and right hemispheres was significantly correlated with BMI. However, there was a positive correlation between the right-left asymmetry index of [11C]raclopride BP in the dorsal putamen and BMI (r=0.43, p<0.05), suggesting that greater BMI is linked with higher receptor availability in the right dorsal putamen relative to the left in non-obese individuals. The present results, combined with previous findings, may also suggest neurochemical mechanisms underlying the regulation of food intake in non-obese individuals.
Body Mass Index* ; Body Weight ; Dopamine* ; Eating ; Humans ; Male ; Positron-Emission Tomography ; Putamen*

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Development of a Touch-Screen-Based Paradigm for Assessing Working Memory in the Mouse.

Chuljung KWAK ; Chae Seok LIM ; Bong Kiun KAANG

Experimental Neurobiology.2015;24(1):84-89. doi:10.5607/en.2015.24.1.84

Assessing the working memory of the rodent by using a touch-screen system has several advantages (e.g., allowing highly accurate data collection and flexibility in memory task design). However, there is currently no available testing paradigm utilizing touch-screen systems that can assess working memory in the mouse. In this study, we developed a touch-screen testing paradigm in which mice were trained to choose a location that is matched to a sample location after a time delay. Consistent with previous studies, this study showed that mice could not only learn the rule in the delayed matched to position (DMTP), but also could retain a transitory memory of the sample position during delay. This indicates that a touch-screen system can provide a DMTP testing platform to assess working memory in the mouse.
Animals ; Data Collection ; Memory ; Memory, Short-Term* ; Mice* ; Pliability ; Rodentia

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Long-term Treatment with Oriental Medicinal Herb Artemisia princeps Alters Neuroplasticity in a Rat Model of Ovarian Hormone Deficiency.

Hyun Bum KIM ; Byeong Jae KWON ; Hyun Ji CHO ; Ji Won KIM ; Jeong Woo CHON ; Moon Ho DO ; Sang Yong PARK ; Sun Yeou KIM ; Sung Ho MAENG ; Yoo Kyoung PARK ; Ji Ho PARK

Experimental Neurobiology.2015;24(1):71-83. doi:10.5607/en.2015.24.1.71

Artemisia princeps (AP) is a flowering perennial used as a traditional medicine and dietary supplement across East Asia. No study has yet assessed its effects on synaptic plasticity in hippocampus and much less in a model of ovarian hormone deficiency. We examined the influence of chronic oral AP ethanol extract treatment in ovariectomized rats on the induction of long-term depression in a representative synapse (CA3-CA1) of the hippocampus. Ovariectomized rats demonstrated lower trabecular mean bone mineral densities than sham, validating the establishment of pathology. Against this background of pathology, AP-treated ovariectomized rats exhibited attenuated long-term depression (LTD) in CA1 relative to water-treated controls as measured by increased field excitatory post-synaptic potentials (fEPSP) activation averages over the post-stimulation period. While pathological significance of long-term depression (LTD) in ovariectomized rats is conflicting, that AP treatment significantly affected its induction offers justification for further study of its influences on plasticity and its related disorders.
Animals ; Artemisia* ; Bone Density ; Depression ; Dietary Supplements ; Ethanol ; Far East ; Female ; Flowers ; Hippocampus ; Medicine, East Asian Traditional ; Medicine, Traditional ; Models, Animal* ; Neuronal Plasticity* ; Ovariectomy ; Pathology ; Plants, Medicinal* ; Plastics ; Rats ; Synapses

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COMP-Ang1 Potentiates EPC Treatment of Ischemic Brain Injury by Enhancing Angiogenesis Through Activating AKT-mTOR Pathway and Promoting Vascular Migration Through Activating Tie2-FAK Pathway.

Hyo Eun MOON ; Kyunghee BYUN ; Hyung Woo PARK ; Jin Hyun KIM ; Jin HUR ; Joong Shin PARK ; Jong Kwan JUN ; Hyo Soo KIM ; Seung Leal PAEK ; In Keyoung KIM ; Jae Ha HWANG ; Jin Wook KIM ; Dong Gyu KIM ; Young Chul SUNG ; Gou Young KOH ; Chang W SONG ; Bonghee LEE ; Sun Ha PAEK

Experimental Neurobiology.2015;24(1):55-70. doi:10.5607/en.2015.24.1.55

Successful recovery from brain ischemia is limited due to poor vascularization surrounding the ischemic zone. Cell therapy with strong angiogenic factors could be an effective strategy to rescue the ischemic brain. We investigated whether cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable and potent Ang1 variant, enhances the angiogenesis of human cord blood derived endothelial progenitor cells (hCB-EPCs) for rescuing brain from ischemic injury. COMP-Ang1 markedly improved the tube formation of capillaries by EPCs and incorporation of EPCs into tube formation with human umbilical vein endothelial cells (HUVECs) upon incubation on matrigel in vitro. COMP-Ang1 stimulated the migration of EPCs more than HUVECs in a scratch wound migration assay. The transplanted EPCs and COMP-Ang1 were incorporated into the blood vessels and decreased the infarct volume in the rat ischemic brain. Molecular studies revealed that COMP-Ang1 induced an interaction between Tie2 and FAK, but AKT was separated from the Tie2-FAK-AKT complex in the EPC plasma membrane. Tie2-FAK increased pp38, pSAPK/JNK, and pERK-mediated MAPK activation and interacted with integrins alphanubeta3, alpha4, beta1, finally leading to migration of EPCs. AKT recruited mTOR, SDF-1, and HIF-1alpha to induce angiogenesis. Taken together, it is concluded that COMP-Ang1 potentiates the angiogenesis of EPCs and enhances the vascular morphogenesis indicating that combination of EPCs with COMP-Ang1 may be a potentially effective regimen for ischemic brain injury salvage therapy.
Angiogenesis Inducing Agents ; Animals ; Blood Vessels ; Brain ; Brain Injuries* ; Brain Ischemia ; Capillaries ; Cartilage Oligomeric Matrix Protein ; Cell Membrane ; Cell- and Tissue-Based Therapy ; Fetal Blood ; Human Umbilical Vein Endothelial Cells ; Humans ; Integrins ; Ischemia ; Morphogenesis ; Rats ; Salvage Therapy ; Stem Cells ; Wounds and Injuries

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Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study.

Juhyun SONG ; Joohyun PARK ; Jae Hwan KIM ; Ja Yong CHOI ; Jae Young KIM ; Kyoung Min LEE ; Jong Eun LEE

Experimental Neurobiology.2015;24(1):41-54. doi:10.5607/en.2015.24.1.41

Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection.
Aquaporins ; Aquaporin 1 ; Ascorbic Acid ; bcl-2-Associated X Protein ; Blood-Brain Barrier ; Brain ; Brain Edema* ; Brain Injuries ; Brain Ischemia* ; Caspase 3 ; Cell Death ; Claudin-5 ; Dehydroascorbic Acid* ; Edema ; Neurons ; Nitric Oxide Synthase Type II ; Oxidative Stress ; Post-Synaptic Density ; Stroke

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Amelioration of Cerebral Ischemic Injury by a Synthetic Seco-nucleoside LMT497.

Sangwoo RYU ; Joonha KWON ; Hyeon PARK ; In Young CHOI ; Sunyoung HWANG ; Veeraswamy GAJULAPATI ; Joo Young LEE ; Yongseok CHOI ; Katia VARANI ; Pier Andrea BOREA ; Chung JU ; Won Ki KIM

Experimental Neurobiology.2015;24(1):31-40. doi:10.5607/en.2015.24.1.31

Recently, we reported that the A3 adenosine receptor (A3AR) agonist LJ529 (2-chloro-N6-(3-iodobnzyl)-5'-N-methylcarbamoyl-4'-thioadenosine) reduces cerebral ischemic injury via inhibition of recruitment of peripheral inflammatory cells into ischemic brain lesion. A3AR agonists, however, are known to possess anti-platelet activity, which may deter the combination therapy with tissue plasminogen activator for the therapy of cerebral ischemic stroke. Thus, the present study investigates the neuroprotective/anti-ischemic effect of a synthetic seco-nucleoside, LMT497 ((S)-2-((R)-1-(2-chloro-6-(3-iodobenzylamino)-9H-purin-9-yl)-2-hydroxyethoxy)-3-hydroxy-N-methylpropanamide) with little anti-platelet activity. LMT497 neither showed A3AR binding activity nor anti-platelet activity. In our present study LMT497 significantly attenuated the injury/death of cortical neurons exposed to oxygen-glucose deprivation (OGD) followed by re-oxygenation (R). LMT497 significantly reduced the ascending cellular level of reactive oxygen species under ischemic conditions by increasing the superoxide dismutase (SOD) levels. LMT497 also inhibited the migration of microglia which mediates inflammatory responses in ischemia. In rats subjected to middle cerebral artery occlusion (MCAO, 1.5 h) followed by reperfusion, LMT497 largely reduced brain infarction volume, and edema, and improved neurological score. Therapeutic efficacy of LMT497 was obtained by twice treatments even at 10 h and 18 h after the onset of ischemia. Collectively, LMT497 could be a therapeutic drug candidate with a wide therapeutic time window for the treatment of cerebral ischemic stroke.
Animals ; Brain ; Brain Infarction ; Brain Ischemia ; Edema ; Infarction, Middle Cerebral Artery ; Inflammation ; Ischemia ; Microglia ; Neurons ; Oxidative Stress ; Rats ; Reactive Oxygen Species ; Receptors, Purinergic P1 ; Reperfusion ; Stroke ; Superoxide Dismutase ; Tissue Plasminogen Activator

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Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model.

Chea Ha KIM ; Jae Seung HONG

Experimental Neurobiology.2015;24(1):24-30. doi:10.5607/en.2015.24.1.24

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level.
Animals ; Blood Glucose* ; CA3 Region, Hippocampal ; Cell Death ; Corticosterone ; Down-Regulation ; Glucose ; Insulin ; Kainic Acid ; Mice* ; Neurons ; Plasma ; Up-Regulation

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Ca2+ Entry is Required for Mechanical Stimulation-induced ATP Release from Astrocyte.

Jaekwang LEE ; Ye Eun CHUN ; Kyung Seok HAN ; Jungmoo LEE ; Dong Ho WOO ; C Justin LEE

Experimental Neurobiology.2015;24(1):17-23. doi:10.5607/en.2015.24.1.17

Astrocytes and neurons are inseparable partners in the brain. Neurotransmitters released from neurons activate corresponding G protein-coupled receptors (GPCR) expressed in astrocytes, resulting in release of gliotransmitters such as glutamate, D-serine, and ATP. These gliotransmitters in turn influence neuronal excitability and synaptic activities. Among these gliotransmitters, ATP regulates the level of network excitability and is critically involved in sleep homeostasis and astrocytic Ca2+ oscillations. ATP is known to be released from astrocytes by Ca2+-dependent manner. However, the precise source of Ca2+, whether it is Ca2+ entry from outside of cell or from the intracellular store, is still not clear yet. Here, we performed sniffer patch to detect ATP release from astrocyte by using various stimulation. We found that ATP was not released from astrocyte when Ca2+ was released from intracellular stores by activation of Galpha(q)-coupled GPCR including PAR1, P2YR, and B2R. More importantly, mechanical stimulation (MS)-induced ATP release from astrocyte was eliminated when external Ca2+ was omitted. Our results suggest that Ca2+ entry, but not release from intracellular Ca2+ store, is critical for MS-induced ATP release from astrocyte.
Adenosine Triphosphate* ; Astrocytes* ; Brain ; Glutamic Acid ; Homeostasis ; Neurons ; Neurotransmitter Agents

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A Critical Role of GIT1 in Vertebrate and Invertebrate Brain Development.

Sung Tae HONG ; Won MAH

Experimental Neurobiology.2015;24(1):8-16. doi:10.5607/en.2015.24.1.8

GIT1, a multifunctional signaling adaptor protein, is implicated in the development of dendritic spines and neuronal synapses. GIT1 forms a signaling complex with PIX, RAC, and PAK proteins that is known to play important roles in brain development. Here we found that Git1-knockout (Git1-/-) mice show a microcephaly-like small brain phenotype, which appears to be caused by reduced neuronal size rather than number. Git1-/- mice also show decreased dendritic spine number without morphological alterations in the hippocampus. Behaviorally, Git1-/- mice show impaired motor coordination and learning and memory. In addition, adult dGit Drosophila mutants show decreased brain size and abnormal morphology of the mushroom body. These results suggest that GIT1 is important for brain development in both rodents and flies.
Adult ; Animals ; Brain* ; Dendritic Spines ; Diptera ; Drosophila ; Hippocampus ; Humans ; Invertebrates* ; Learning ; Memory ; Mice ; Microcephaly ; Mushroom Bodies ; Neurons ; Phenotype ; Rodentia ; Synapses ; Vertebrates*

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Prion-like Mechanism in Amyotrophic Lateral Sclerosis: are Protein Aggregates the Key?.

Shynrye LEE ; Hyung Jun KIM

Experimental Neurobiology.2015;24(1):1-7. doi:10.5607/en.2015.24.1.1

ALS is a fatal adult-onset motor neuron disease. Motor neurons in the cortex, brain stem and spinal cord gradually degenerate in ALS patients, and most ALS patients die within 3~5 years of disease onset due to respiratory failure. The major pathological hallmark of ALS is abnormal accumulation of protein inclusions containing TDP-43, FUS or SOD1 protein. Moreover, the focality of clinical onset and regional spreading of neurodegeneration are typical features of ALS. These clinical data indicate that neurodegeneration in ALS is an orderly propagating process, which seems to share the signature of a seeded self-propagation with pathogenic prion proteins. In vitro and cell line experimental evidence suggests that SOD1, TDP-43 and FUS form insoluble fibrillar aggregates. Notably, these protein fibrillar aggregates can act as seeds to trigger the aggregation of native counterparts. Collectively, a self-propagation mechanism similar to prion replication and spreading may underlie the pathology of ALS. In this review, we will briefly summarize recent evidence to support the prion-like properties of major ALS-associated proteins and discuss the possible therapeutic strategies for ALS based on a prion-like mechanism.
Amyotrophic Lateral Sclerosis* ; Brain Stem ; Cell Line ; Humans ; Motor Neuron Disease ; Motor Neurons ; Pathology ; Prions ; Respiratory Insufficiency ; Spinal Cord

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