• Molecules and Cells
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• v.45 no.8
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• pp.537-549
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• 2022

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

• Molecules and Cells
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• v.40 no.3
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• pp.163-168
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• 2017

Microglia are the primary resident immune cells of the central nervous system (CNS). They are the first line of defense of the brain's innate immune response against infection, injury, and diseases. Microglia respond to extracellular signals and engulf unwanted neuronal debris by phagocytosis, thereby maintaining normal cellular homeostasis in the CNS. Pathological stimuli such as neuronal injury induce transformation and activation of resting microglia with ramified morphology into a motile amoeboid form and activated microglia chemotax toward lesion site. This review outlines the current research on microglial activation and chemotaxis.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.613-617
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• 2001

The present study examined the hypothesis that NMDA, AMPA/Kainate, and metabotropic (mGlu) glutamate receptors contribute to a behavioral stimulation induced by activation of dopamine receptors by comparing responses in apomorphine-induced cage climbing behaviors in mice. MK-801, CNQX, and MCPG were served as the NMDA receptor, AMPA/Kainate receptor, and mGlu receptor antagonist, respectively, to elucidate the glutamatergic modulation in apomorphine-induced eopaminergic activation in mice. Drugs were administered intracerebroventricularly (i.c.v.) into the mouse brain 15 min before the apomorphine treatment (2 mg/kg, s.c.). 1.c.v. injection of MK-801 inhibited the apomorphine-induced cage climbing behavior dose-dependently. However, treatments with CNQX and MCPG did not any significant change in apomorphine-induced cage climbing behavior in mice. These results suggest that stimulation of NMDA type of glutamate receptors could contribute to the dopaminergic sti mutation, but not AMPA/Kainate and mGlu type glutamate receptors.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.302-306
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• 2015

VvpM, one of the extracellular metalloproteases produced by Vibrio vulnificus, induces apoptotic cell death via a pathway consisting of ERK activation, cytochrome c release, and activation of caspases-9 and -3. VvpM-treated cells also showed necrotic cell death as stained by propidium iodide (PI). The percentage of PI-stained cells was decreased by pretreatment with Necrostatin-1, indicating that VvpM-mediated cell death occurs through necroptosis. The appearance of autophagic vesicles and lipidated form of light-chain-3B in rVvpM-treated cells suggests an involvement of autophagy in this process. Therefore, the multifarious action of VvpM might be one of the factors responsible for V. vulnificus pathogenesis.

• BMB Reports
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• v.49 no.7
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• pp.370-375
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• 2016

Ras oncoproteins are small molecular weight GTPases known for their involvement in oncogenesis, which operate in a complex signaling network with multiple effectors. Approximately 25% of human tumors possess mutations in a member of this family. The Raf1/MEK/Erk1/2 pathway is one of the most intensively studied signaling mechanisms. Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases in a cell type- and stimuli-dependent manner. In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway. We also demonstrated, by applying pharmacological inhibitors and effector mutants of Ras, that induction of MKP3 at the protein level is positively regulated by the oncogenic Ras/Raf/MEK/Erk1/2 signaling pathway.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.67-67
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• 2003

Minocycline is known to protect neurons from microglia-mediated cell death in many experimental models of brain diseases including ischemic stroke, Huntingtons disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury, multiple sclerosis, and Parkinsons disease. When the activity of caspases was assessed using their fluorescent peptide substrates, activation of caspase-2, 3, 8, and 9 was evident within 2 8 hr following oxidative insult with 0.5 mM hydrogen peroxide in PC12 cells. Minocycline significantly attenuated activation of these caspases up to 18 hr, resulting a significant increase in the cell viability as assessed by MTT assay as well as trypan blue staining. However, cleavage of alpha-spectrin and a cdk5 activator p35, which are known to be substrates for calpain, remained unchanged in the presence of minocycline, suggesting that minocycline did not block caspase-3-independent cell death or necrosis. Moreover, co-treatment with minocycline and a calpain inhibitor calpeptin synergistically inhibited hydrogen peroxide-induced cell death. These data suggest that minocycline directly inhibited apoptosis, but not necrosis, after oxidative insult in PC12 cells.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.467-473
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• 2014

The purpose of this study is to investigate the memory enhancing effect and underlying molecular mechanism of arabinoxylan (AX), a major component of dietary fiber in wheat against scopolamine (SCO)-induced amnesia in Sprague-Dawley (SD) rats. Diverse behavior tests including Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. SCO significantly decreased the spontaneous alterations in Y-maze test and step-through latency in passive avoidance test, whereas increased time spent to find the hidden platform in Morris water maze test compared with the sham control group. In contrast, oral administration of AX (25 mg/kg and 50 mg/kg) effectively reversed the SCO-induced cognitive impairments in SD rats. Furthermore, AX treatment up-regulated the expression of brain-derived neurotrophic factor (BDNF) in the cortex and hippocampus via promoting activation of cAMP response element binding protein (CREB). Therefore, our findings suggest that AX can improve SCO-induced learning and memory impairment possibly through activation of CREB and up-regulation of BDNF levels, thereby exhibiting a cognition-enhancing potential.

• Korean Journal of Biological Psychiatry
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• v.18 no.1
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• pp.15-24
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• 2011

Mood disorder is unlikely to be a disease of a single brain region or a neurotransmitter system. Rather, it is now generally viewed as a multidimensional disorder that affects many neural pathways. Growing neuroimaging evidence suggests the anterior cingulate-pallidostriatal-thalamic-amygdala circuit as a putative cortico-limbic mood regulating circuit that may be dysfunctional in mood disorders. Brain-imaging techniques have shown increased activation of mood-generating limbic areas and decreased activation of cortical areas in major depressive disorder(MDD). Furthermore, the combination of functional abnormalities in limbic subcortical neural regions implicated in emotion processing together with functional abnormalities of prefrontal cortical neural regions probably result in the emotional lability and impaired ability to regulate emotion in bipolar disorder. Here we review the biological correlates of MDD and bipolar disorder as evidenced by neuroimaging paradigms, and interpret these data from the perspective of endophenotype. Despite possible limitations, we believe that the integration of neuroimaging research findings will significantly advance our understanding of affective neuroscience and provide novel insights into mood disorders.

• Anxiety and mood
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• v.4 no.2
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• pp.127-134
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• 2008

Objective : This study examined whether major depressive disorder patients with anxiety traits displayed abnormal electroencephalographic (EEG) alpha asymmetries. Methods : Resting EEG was recorded in 11 outpatients with major depressive disorder (6 of whom had a high anxiety trait while 5 exhibited a low anxiety trait) and 6 controls. Results : In contrast to the controls, within the major depressive disorder patient group, comorbid anxiety disorder showed alpha asymmetry indicative of less activation over right than over left temporal sites. Patients diagnosed with major depressive disorder but no anxiety disorder showed a reduced temporal alpha asymmetry, supporting the potential importance of evaluating anxiety in studies of regional brain activation, in depressed patients. Conclusion : These findings suggest that anxiety is associated with brain hypoactivation, especially with right temporal hypoactivation.

• The Journal of Korean Physical Therapy
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• v.22 no.2
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• pp.7-13
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• 2010

Purpose: This study was designed to determine the correlation between faster response time and functional activities of brain regions during cognitive time management. Methods: Twelve healthy subjects participated in this experiment. Subjects performed the serial reaction time task (SRTT), which was designed by the Superlab program, during fMRI scanning. When the 'asterisk' appeared in the 4 partition spaces on the monitor, the subject had to press the correct response button as soon as possible. Results: fMRI results showed activation of the left primary sensorimotor cortex, both premotor areas, the supplementary motor area, posterior parietal cortex and cerebellum. There were significant correlations, from moderate to strong, between faster reaction time and BOLD signal intensity in activated areas. Conclusion: These results suggest that motor skill learning to be needed cognitive time management is associated with greater activation of large scale sensorimotor networks.