Astrocytic control of synaptic NMDA receptors : Astrocytic control of synaptic NMDA receptors

Lee, C. Justin,Mannaioni, Guido,Yuan, Hongjie,Woo, Dong Ho,Gingrich, Melissa B.,Traynelis, Stephen F. Cambridge University Press 2007 The Journal of physiology Vol.581 No.3

Ca ²⁺ Entry is Required for Mechanical Stimulation-induced ATP Release from Astrocyte

Lee, Jaekwang,Chun, Ye-Eun,Han, Kyung-Seok,Lee, Jungmoo,Woo, Dong Ho,Lee, C. Justin The Korean Society for Brain and Neural Science 2015 Experimental Neurobiology Vol.24 No.1

<P>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 Ca<SUP>2+</SUP> oscillations. ATP is known to be released from astrocytes by Ca<SUP>2+</SUP>-dependent manner. However, the precise source of Ca<SUP>2+</SUP>, whether it is Ca<SUP>2+</SUP> 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 Ca<SUP>2+</SUP> was released from intracellular stores by activation of Gα<SUB>q</SUB>-coupled GPCR including PAR1, P2YR, and B2R. More importantly, mechanical stimulation (MS)-induced ATP release from astrocyte was eliminated when external Ca<SUP>2+</SUP> was omitted. Our results suggest that Ca<SUP>2+</SUP> entry, but not release from intracellular Ca<SUP>2+</SUP> store, is critical for MS-induced ATP release from astrocyte.</P>

Reactive astrocytes as the cause of Alzheimer’s disease

C. Justin Lee 한국실험동물학회 2023 한국실험동물학회 학술발표대회 논문집 Vol.2023 No.2

Attenuated Glial K ⁺ Clearance Contributes to Long-Term Synaptic Potentiation Via Depolarizing GABA in Dorsal Horn Neurons of Rat Spinal Cord

Lee, Jaekwang,Favorov, Oleg V,Tommerdahl, Mark,Lee, C. Justin,Whitsel, Barry L. The Korean Society for Brain and Neural Science 2014 Experimental Neurobiology Vol.23 No.1

<P>It has been reported that long-term enhancement of superficial dorsal horn (DH<SUB>s</SUB>) excitatory synaptic transmission underlies central sensitization, secondary hyperalgesia, and persistent pain. We tested whether impaired clearance of K<SUP>+</SUP> and glutamate by glia in DH<SUB>s</SUB> may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities. Transient exposure of the spinal cord slice to fluorocitrate (FC) is shown to be accompanied by a protracted <I>decrease</I> of the DH<SUB>s</SUB> optical response to repetitive electrical stimulation of the ipsilateral dorsal root, and by a similarly protracted <I>increase</I> in the postsynaptic response of the DH<SUB>s</SUB> like LTP. It also is shown that LTP<SUB>FC</SUB><I>does not</I> occur in the presence of APV, and becomes progressively <I>smaller</I> as [K<SUP>+</SUP>]<SUB>o</SUB> in the perfusion solution decreased from 3.0 mM to 0.0 mM. Interestingly LTP<SUB>FC</SUB> is <I>reduced</I> by bath application of Bic. Whole-cell patch recordings were carried out to evaluate the effects of FC on the response of DH<SUB>s</SUB> neurons to puffer-applied GABA. The observations reveal that transient exposure to FC is reliably accompanied by a prolonged (>1 hr) depolarizing shift of the equilibrium potential for the DH<SUB>s</SUB> neuron transmembrane ionic currents evoked by GABA. Considered collectively, the findings demonstrate that LTP<SUB>FC</SUB> involves (1) elevation of [K<SUP>+</SUP>]<SUB>o</SUB> in the DH<SUB>s</SUB>, (2) NMDAR activation, and (3) conversion of the effect of GABA on DH<SUB>s</SUB> neurons from inhibition to excitation. It is proposed that a transient impairment of astrocyte energy production can trigger the cascade of dorsal horn mechanisms that underlies hyperalgesia and persistent pain.</P>

Effect of proton irradiation on the structural and electrochemical properties of MnO₂ nanosheets

Lee, Won-Gil,Jang, Hyun Seok,Justin Raj, C.,Rajesh, Murugesan,Kim, Byung Chul,Cho, Won-Je,Yu, Kook Hyun Elsevier 2018 Journal of electroanalytical chemistry Vol.811 No.-

<P><B>Abstract</B></P> <P>K-birnessite type MnO<SUB>2</SUB> (δ-MnO<SUB>2</SUB>) nanosheets were synthesized via hydrothermal technique and investigated the influence of proton beam irradiations on their structural and electrochemical properties. The effect of various proton beam irradiation conditions (proton energy and dose) on MnO<SUB>2</SUB> nanosheets were studied using X-ray diffraction, SEM, TEM, UV absorption, X-ray photoelectron spectroscopy and Raman spectral analysis. The proton irradiation displayed considerable structural transformation from δ-MnO<SUB>2</SUB> to α-MnO<SUB>2</SUB>/δ-MnO<SUB>2</SUB> and the morphology from nanosheets to distorted nanotubes. The electrochemical properties of the samples were analyzed using cyclic voltammetry, galvanostatic charge/discharge test and impedance spectroscopic techniques. The sample showed a comparable improvement in the specific capacitance value up to a certain extent of proton irradiation. The MnO<SUB>2</SUB> nanosheets irradiated with proton energy of 7.8 MeV and dose 10<SUP>14</SUP> p cm<SUP>−2</SUP> exhibited a maximum specific capacitance value of 159 Fg<SUP>−1</SUP>. But, the sample irradiated with high proton energy (9.8 MeV) and dose (10<SUP>16</SUP> p cm<SUP>−2</SUP>) showed 114 Fg<SUP>−1</SUP> specific capacitance which is much less than that of unirradiated sample (142 Fg<SUP>−1</SUP>).</P> <P><B>Highlights</B></P> <P> <UL> <LI> Investigated the effect of various energy and dose of proton beam irradiations on δ-MnO<SUB>2</SUB> nanosheets. </LI> <LI> The proton irradiation showed a structural and morphological change in δ-MnO<SUB>2</SUB>. </LI> <LI> The electrochemical performances were slightly improved with respect to irradiation up to a certain extent. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A multichannel neural probe with embedded microfluidic channels for simultaneous in vivo neural recording and drug delivery.

Lee, Hyunjoo J,Son, Yoojin,Kim, Jeongyeon,Lee, C Justin,Yoon, Eui-Sung,Cho, Il-Joo Royal Society of Chemistry 2015 Lab on a chip Vol.15 No.6

<P>Multi-functional neural probes integrated with various stimulation modalities are becoming essential tools in neuroscience to study the brain more effectively. In this paper, we present a new multi-functional neural probe that allows chemical stimulation through drug delivery and simultaneous recording of individual neuron signals through a microelectrode array. By embedding microchannels in silicon using a proposed glass reflow process, we successfully fabricated 40 μm thick silicon neural probes suitable for small animal experiments. The electrochemical impedance spectroscopy confirms that impedance of iridium microelectrodes is low enough (<1 Mω at 1 kHz) to measure neural signals. Flow rate characterization in a 0.9% w/v agarose gel shows the capability to deliver a small volume of drugs (<1 μl) at a controlled flow rate. We demonstrate the viability and potential of this new probe by conducting in vivo experiments on mice. Because of the proposed compact structure, both action potentials of individual neurons and local field potentials (LFP) at the thalamus region of a mouse brain were successfully detected with a noise level of ~30 μVpp. Furthermore, we successfully induced absence seizure by injecting seizure-inducing drugs (baclofen) at a local target region and observed distinctive changes in neural signal patterns. Specifically, spike-wave discharge (SWD), which is an indicative signal pattern of absence seizure, was successfully recorded. These signals were also directly compared to SWD detected after inducing absence seizure through direct injection of baclofen through the abdomen. This work demonstrates the potential of our multi-functional neural probes for use in effective investigation of brain functions and disorders by using widely available mouse models.</P>

GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear renewal

Lee, Sukwon,Song, Beomjong,Kim, Jeongyeon,Park, Kyungjoon,Hong, Ingie,An, Bobae,Song, Sangho,Lee, Jiwon,Park, Sungmo,Kim, Jihye,Park, Dongeun,Lee, C Justin,Kim, Kyungjin,Shin, Ki Soon,Tsien, Richard W Nature Publishing Group, a division of Macmillan P 2013 NATURE NEUROSCIENCE Vol.16 No.10

Fear renewal, a widely pursued model of post-traumatic stress disorder and phobias, refers to the context-specific relapse of conditioned fear after extinction. However, its molecular mechanisms are largely unknown. We found that renewal-inducing stimuli, generally believed to be insufficient to induce synaptic plasticity, enhanced excitatory synaptic strength, activity of synaptic GluA2-lacking AMPA receptors and Ser831 phosphorylation of synaptic surface GluA1 in the lateral nucleus of the amygdala (LAn) of fear-extinguished rats. Consistently, the induction threshold for LAn synaptic potentiation was considerably lowered after extinction, and renewal occluded this low-threshold potentiation. The low-threshold potentiation (a potential cellular substrate for renewal), but not long-term potentiation, was attenuated by dialysis into LAn neurons of a GluA1-derived peptide that competes with Ser831-phosphorylated GluA1. Microinjections of the same peptide into the LAn attenuated fear renewal, but not fear learning. Our findings suggest that GluA1 phosphorylation constitutes a promising target for clinical treatment of aberrant fear-related disorders.

Generation of mtDNA Homoplasmic Cloned Lambs

Lee, Joon-Hee,Peters, Amy,Fisher, Pat,Bowles, Emma J.,St. John, Justin C.,Campbell, Keith H. S. Mary Ann Liebert 2010 Cellular reprogramming Vol.12 No.3

<P>Abstract Generally in mammals, individual animals contain only maternally inherited mitochondrial DNA (mtDNA), as paternal (sperm)-derived mitochondria are usually eliminated during early development. Somatic cell nuclear transfer (SCNT) bypasses the normal routes of mtDNA inheritance and introduces not only a different nuclear genome into the recipient cytoplast (in general an enucleated oocyte) but also somatic mitochondria. Differences in mtDNA genotype between recipient oocytes and potential mtDNA heteroplasmy due to persistence and replication of somatic mtDNA means that offspring generated by SCNT are not true clones. However, more importantly, the consequences of the presence of somatic mtDNA, mtDNA heteroplasmy, or possible incompatibility between nuclear and mtDNA genotypes on subsequent development and function of the embryo, fetus and offspring are unknown. Following sexual reproduction, mitochondrial function requires the biparental control of maternally inherited mtDNA, whereas following SCNT incompatibility between the recipient cell mitochondrial and transplanted nuclear genomes, or mtDNA heteroplasmy, may result in energy imbalance and initiate the onset of mtDNA-type disease, or disruption of normal developmental events. To remove the potentially adverse effects of somatic mtDNA following SCNT we have previously produced embryos using donor cells depleted to residual levels of mtDNA (mtDNA(R)). We now report that these cells support development to term and produced live lambs in which no donor somatic mtDNA was detected, the lambs being homoplasmic for recipient oocyte DNA.</P>

<i>Drosophila</i> Atlastin regulates the stability of muscle microtubules and is required for synapse development

Lee, Mihye,Paik, Sang Kyoo,Lee, Min-Jung,Kim, Yoon-Jung,Kim, Sungdae,Nahm, Minyeop,Oh, Soo-Jin,Kim, Hyun-Man,Yim, Jeongbin,Lee, C. Justin,Bae, Yong Chul,Lee, Seungbok Elsevier 2009 Developmental Biology Vol.330 No.2

<P><B>Abstract</B></P><P>Hereditary spastic paraplegia (HSP) is an inherited neurological disorder characterized by progressive spasticity and weakness of the lower extremities. The most common early-onset form of HSP is caused by mutations in the human gene that encodes the dynamin-family GTPase Atlastin-1 (Atl-1). Recently, loss of the <I>Drosophila</I> ortholog of Atl-1 (Atl) has been found to induce locomotor impairments from the earliest adult stages, suggesting the developmental role of atlastin-subfamily GTPases. Here, we provide evidence that Atl is required for normal growth of muscles and synapses at the neuromuscular junction (NMJ). Atl protein is highly expressed in larval body-wall muscles. Loss-of-function mutations in the <I>atl</I> gene reduce the size of muscles and increase the number of synaptic boutons. Rescue of these defects is accomplished by muscular, but not neuronal expression of Atl. Loss of Atl also disrupts ER and Golgi morphogenesis in muscles and reduces the synaptic levels of the scaffold proteins Dlg and α-spectrin. We also provide evidence that Atl functions with the microtubule-severing protein Spastin to disassemble microtubules in muscles. Finally, we demonstrate that the microtubule-destabilizing drug vinblastine alleviates synapse and muscle defects in <I>atl</I> mutants. Together, our results suggest that Atl controls synapse development and ER and Golgi morphogenesis by regulating microtubule stability.</P>

Phase 4 Study in Patients From Asia With Gastroesophageal Reflux Disease Treated With Dexlansoprazole

( Justin C Y Wu ),( Bor-shyang Sheu ),( Ming-shiang Wu ),( Yong Chan Lee ),( Myung-gyu Choi ) 대한소화기 기능성질환·운동학회 2020 Journal of Neurogastroenterology and Motility (JNM Vol.26 No.1

Background/Aims Since the use of dexlansoprazole in Asian subjects with gastroesophageal reflux disease (GERD) has not been adequately characterized, this study was conducted to evaluate the efficacy and safety of dexlansoprazole modified-release in Asian subjects with non-erosive reflux disease (NERD) and erosive esophagitis (EE). Methods In this phase 4, open-label, non-randomized, uncontrolled, multicenter, multi-country study sponsored by Takeda, subjects aged ≥ 20 years with persistent typical GERD symptoms for at least 6 months underwent endoscopy. Based on endoscopic findings, they were assigned to either dexlansoprazole modified-release 30 mg once-daily for 4 weeks (NERD group) or dexlansoprazole modified-release 60 mg once-daily for 8 weeks (EE group). The primary endpoint was the percentage of days that subjects did not experience any 24- hour heartburn or acid regurgitation. Results Of the 445 subjects screened from Hong Kong, South Korea, and Taiwan, 208 were enrolled in the NERD group (mean age: 53.6 years, male: 34.6%) and 88 in the EE group (mean age: 51.7 years, male: 55.7%). Over the treatment period, the median percentage of days that subjects did not experience any 24-hour heartburn or acid regurgitation was 26.9% and 65.5% in the NERD and EE groups, respectively; for nighttime heartburn or acid regurgitation the proportions were 59.3% and 83.3%, respectively. The treatment was well tolerated with low incidence of treatment-related adverse events in NERD and EE groups (6.7% and 5.7%, respectively). Conclusion In Asian patients with GERD, treatment with dexlansoprazole modified-release indicates a favorable efficacy and safety profile in relieving heartburn and acid regurgitation symptoms.