• The Korean Journal of Physiology and Pharmacology
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• v.11 no.3
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• pp.79-84
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• 2007

Because synaptic refinement of medial nucleus of trapezoid body (MNTB) - lateral superior olive (LSO) synapses is most active during the first postnatal week and the long term depression (LTD) has been suggested as one of its mechanisms, LTD of MNTB-LSO synapses was investigated in neonatal rat brain stem slices with the whole cell voltage clamp technique. In $Mg^{2+}$ free condition, tetanus (10 stimuli at 10 Hz for 2 min) in the current clamp mode induced a robust LTD of isolated D, L-APV-sensitive postsynaptic currents (PSCs) for more than 30 min ($n=6,\;2.4{\pm}0.4%$ of the control), while isolated CNQX-sensitive PSCs were not suppressed ($n=6,\;95.3{\pm}1.6%$). Tetanus also elicited similar LTD in the isolated GABAergic/glycinergic PSCs ($n=6,\;3.6{\pm}0.5%$) and mixed PSCs (GABAergic/glycinergic/glutamatergic) ($n=4,\;2.2{\pm}0.7%$). However, such a strong LTD was not observed in the mixed PSCs when 10 mM EGTA was added in the internal solution (n=10), indicating that postsynaptic $Ca^{2+}$ rise is needed for the strong LTD. This robust LTD might contribute to the active synaptic refinement occurring during the first postnatal week.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.23 no.2
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• pp.49-56
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• 2012

Methylphenidate is a widely used stimulant for treatment of attention-deficit hyperactivity disorder (ADHD). In addition to core symptoms of attention and behavioral symptoms, methylphenidate is even effective for executive functions. However, abuse and misuse of stimulants, including methylphenidate, for the purpose of cognitive enhancement is an issue of concern worldwide. Some prejudices and misunderstandings against methylphenidate are popular ; however, little attention has been given to the neuropsychiatric evidence of methylphenidate for enhancement of cognitive function among healthy populations. In this article, our aim was to conduct a review of previous studies investigating the effect of methylphenidate in healthy populations. Findings from several recent studies have demonstrated the effectiveness of methylphenidate for enhancement of cognitive function in healthy populations. The mechanisms of cognitive enhancement are thought to be associated with motivation and the reward circuit in the brain. However, when considering the risk to benefit, an official discussion of the use of methylphenidate among healthy members of the population would be premature. Instead, investigation of epidemiological studies of the prevalence of misuse of stimulants among healthy members of the population, particularly adolescents and college students, is needed. In addition, based on achievements reported in previous studies, investigation of the effect of an approach using non-pharmacological enhancing motivation, which will in turn result in increased cognitive function would be helpful.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.31 no.3
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• pp.105-120
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• 2020

Although autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, patients with ASD frequently manifest atypical sensory behaviors. Recently, atypical sensory perception in ASD has received much attention, yet little is known about its cause or neurobiology. Herein, we review the findings from neuroimaging studies related to visual perception in ASD. Specifically, we examined the neural underpinnings of visual detection, motion perception, and face processing in ASD. Results from neuroimaging studies indicate that atypical visual perception in ASD may be influenced by attention or higher order cognitive mechanisms, and atypical face perception may be affected by disrupted social brain network. However, there is considerable evidence for atypical early visual processing in ASD. It is likely that visual perceptual abnormalities are independent of deficits of social functions or cognition. Importantly, atypical visual perception in ASD may enhance difficulties in dealing with complex and subtle social stimuli, or improve outstanding abilities in certain fields in individuals with Savant syndrome. Thus, future research is required to elucidate the characteristics and neurobiology of autistic visual perception to effectively apply these findings in the interventions of ASD.

• BMB Reports
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• v.51 no.1
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• pp.5-13
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• 2018

Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including $amlyoid-{\beta}$, tau, ${\alpha}-synuclein$, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs.

• BMB Reports
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• v.53 no.1
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• pp.10-19
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• 2020

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnormal inflammation precedes the outbreak of the disease, non-invasive and readily available peripheral inflammatory biomarkers should be considered as possible biomarkers for early diagnosis of AD. In this minireview, we introduce the peripheral biomarker candidates related to abnormal inflammation in AD and discuss their possible molecular mechanisms. Furthermore, we also summarize the current state of inflammatory biomarker research in clinical practice and molecular diagnostics. We believe this review will provide new insights into biomarker candidates for the early diagnosis of AD with systemic relevance to inflammation during AD pathogenesis.

• Journal of Yeungnam Medical Science
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• v.19 no.2
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• pp.136-143
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• 2002

Even though the nonketotic hyperglycemia is a metabolic disorder, it complicates hemichorea-hemiballism rarely. Moreover, generalized chorea-ballism associated with nonketotic hyperglycemia in diabetes mellitus is very rare, so it has not been reported in Korean literature. Although the precise pathophysiologic mechanisms of these disorders are still poorly understood, deficiency of gamma aminobutyric acid (GABA) in nonketotic hyperglycemia or reduced GABAnergic inhibition by striatal lesion may increase inhibitory output to subthalamic nucleus. These result loss of pallidal inhibition and produce contralateral hemichorea-hemiballism. The striatal lesions, such as transient ischemia with reactive astrocytosis or small amount of petechial hemorrhage, are related with changes of magnetic resonance image (MRI) findings presumably. We report a diabetic old woman who developed generalized chorea-ballismus as a very rare complication of nonketotic hyperglycemia. Her brain MRI showed high signal intensity in left lentiform nucleus and right pallidum on T1 weighted images and low signal intensity in bilateral putamen on T2 weighted images with highly enhanced corresponding lesions on T1 weighted enhancement images.

• Molecules and Cells
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• v.37 no.5
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• pp.357-364
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• 2014

Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.

• BioChip Journal
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• v.12 no.4
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• pp.257-267
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• 2018

Inertial microfluidics has attracted significant attention in recent years due to its superior benefits of high throughput, precise control, simplicity, and low cost. Many inertial microfluidic applications have been demonstrated for physiological sample processing, clinical diagnostics, and environmental monitoring and cleanup. In this review, we discuss the fundamental mechanisms and principles of inertial migration and Dean flow, which are the basis of inertial microfluidics, and provide basic scaling laws for designing the inertial microfluidic devices. This will allow end-users with diverse backgrounds to more easily take advantage of the inertial microfluidic technologies in a wide range of applications. A variety of recent applications are also classified according to the structure of the microchannel: straight channels and curved channels. Finally, several future perspectives of employing fluid inertia in microfluidic-based cell sorting are discussed. Inertial microfluidics is still expected to be promising in the near future with more novel designs using various shapes of cross section, sheath flows with different viscosities, or technologies that target micron and submicron bioparticles.

• Parasites, Hosts and Diseases
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• v.57 no.2
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• pp.101-115
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• 2019

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

• Journal of Integrative Natural Science
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• v.15 no.4
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• pp.179-186
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• 2022

The c-Jun N-terminal kinase (JNK3) play major role in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, cerebral ischemia and other Central Nervous System disorders. Since JNK3 is primarily stated in the brain and stimulated by stress-stimuli, this situation is conceivable that inhibiting JNK3 could be a possible treatment for the mechanisms underlying neurodegenerative diseases. In this study drugs from Zinc15 database were screened to identify the JNK3 inhibitors by Molecular docking and Density functional theory approach. Molecular docking was done by Autodock vina and the ligands were selected based on the binding affinity. Our results identified top ten novel ligands as potential inhibitors against JNK3. Molecular docking revealed that Venetoclax, Fosaprepitant and Avapritinib exhibited better binding affinity and interacting with proposed binding site residues of JNK3. Density functional theory was used to compute the values for energy gap, lowest unoccupied molecular orbital (LUMO), and highest occupied molecular orbital (HOMO). The results of Density functional theory study showed that Venetoclax, Fosaprepitant and Avapritinib serves as a lead compound for the development of JNK3 small molecule inhibitors.