남형식 교수

The underlying mechanisms of how positive emotional valence (e.g., pleasure) causes preference of an associated context is poorly understood. Here, we show that activation of astrocytic μ-opioid receptor (MOR) drives conditioned place preference (CPP) by means of specific modulation of astrocytic MOR, an exemplar endogenous Gi protein-coupled receptor (Gi-GPCR), in the CA1 hippocampus. Long-term potentiation (LTP) induced by a subthreshold stimulation with the activation of astrocytic MOR at the

Glucose hypometabolism in cortical structures after functional disconnection is frequently reported in patients with white matter diseases such as subcortical stroke. However, the molecular and cellular mechanisms have been poorly elucidated. Here we show, in an animal model of internal capsular infarct, that GABA-synthesizing reactive astrocytes in distant cortical areas cause glucose hypometabolism via tonic inhibition of neighboring neurons. We find that reversal of aberrant astrocytic GABA s

To develop novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC₅₀ value of 28 nM with no apparent effect on MAO-A activity at 10 μM. Based on the

Monoamine oxidase-B (MAOB) has been believed to mediate the degradation of monoamine neurotransmitters such as dopamine. However, this traditional belief has been challenged by demonstrating that it is not MAOB but MAOA which mediates dopamine degradation. Instead, MAOB mediates the aberrant synthesis of GABA and hydrogen peroxide (H₂O₂) in reactive astrocytes of Parkinson's disease (PD). Astrocytic GABA tonically suppresses the dopaminergic neuronal activity, whereas H<sub

Reactive astrogliosis is a hallmark of Alzheimer's disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on th

µ-opioid receptor (MOR) is a class of opioid receptors with a high affinity for enkephalins and beta-endorphin. In hippocampus, activation of MOR is known to enhance the neuronal excitability of pyramidal neurons, which has been mainly attributed to a disinhibition of pyramidal neurons via activating Gαi subunit to suppress the presynaptic release of GABA in hippocampal interneurons. In contrast, the potential role of MOR in hippocampal astrocytes, the most abundant cell type in the brain, has r

Mutations in specific genes, including synuclein alpha (<i>SNCA</i>) that encodes the α-synuclein protein, are known to be risk factors for sporadic Parkinson's disease (PD), as well as critical factors for familial PD. In particular, A53T-mutated <i>SNCA</i> (A53T-SNCA) is a well-studied familial pathologic mutation in PD. However, techniques for deletion of the mutated <i>SNCA</i> gene <i>in vivo</i> have not been developed. Here, we used the CRISPR-Cas9 system to delete A53T-SNCA <i>in vitro<

Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson's disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 ex

Hydrogels have garnered significant interest in the biomedical field owing to their tissue-like properties and capability to incorporate various fillers. Among these, injectable hydrogels have been highlighted for their unique advantages, especially their minimally invasive administration mode for implantable use. These injectable hydrogels can be utilized in their pristine forms or as composites by integrating them with therapeutic filler materials. Given their primary application in implantabl

(Cell Reports 32, 107861-1–14.e1–e7; July 7, 2020) In the originally published version of this article, the author name Jung Moo Lee was spelled incorrectly. This has now been corrected online. The authors regret this error. Excessive Astrocytic GABA Causes Cortical Hypometabolism and Impedes Functional Recovery after Subcortical StrokeNam et al.Cell ReportsJuly 07, 2020In BriefNam et al. demonstrate that excessive GABA from reactive astrocytes accounts for cortical glucose hypometabolism follow

Although it was believed that the brain was incapable of regeneration after embryonic development, neurogenesis is now known to occur into adulthood. Adult neurogenesis has been demonstrated in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. Acupuncture has long been used to treat neurologic conditions, and recent reports suggest that neurogenesis may account for its beneficial effects. ST36 was the most often used acupoint in p

The primo vascular systems (PVS) observed in the central nervous system have been limited to the ones floating in the cerebrospinal fluid. In those experiments, it was difficult to obtain the same results because the PVS was not fixed in a given anatomical position. In the current work, we report a finding of a PVS in a well-defined location, namely, underneath the superior sagittal sinus in the sagittal fissure, so that repetition of the experiments is possible. This provides a cornerstone for

High 11 C-ACE uptake is associated with high-grade IDH1 -wt tumors, thus facilitating differentiation from high-grade IDH1-mt and low-grade gliomas. In particular, low 11 C-ACE uptake in ODs is advantageous in overcoming the limitation of radiolabeled amino acid tracers.