• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.272-287
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• 2019

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.

• Journal of Yeungnam Medical Science
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• v.36 no.3
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• pp.183-191
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• 2019

Some patients with type 1 and type 2 diabetes mellitus (DM) present with cognitive dysfunctions. The pathophysiology underlying this complication is not well understood. Type 1 DM has been associated with a decrease in the speed of information processing, psychomotor efficiency, attention, mental flexibility, and visual perception. Longitudinal epidemiological studies of type 1 DM have indicated that chronic hyperglycemia and microvascular disease, rather than repeated severe hypoglycemia, are associated with the pathogenesis of DM-related cognitive dysfunction. However, severe hypoglycemic episodes may contribute to cognitive dysfunction in high-risk patients with DM. Type 2 DM has been associated with memory deficits, decreased psychomotor speed, and reduced frontal lobe/executive function. In type 2 DM, chronic hyperglycemia, long duration of DM, presence of vascular risk factors (e.g., hypertension and obesity), and microvascular and macrovascular complications are associated with the increased risk of developing cognitive dysfunction. The pathophysiology of cognitive dysfunction in individuals with DM include the following: (1) role of hyperglycemia, (2) role of vascular disease, (3) role of hypoglycemia, and (4) role of insulin resistance and amyloid. Recently, some investigators have proposed that type 3 DM is correlated to sporadic Alzheimer's disease. The molecular and biochemical consequences of insulin and insulin-like growth factor resistance in the brain compromise neuronal survival, energy production, gene expression, plasticity, and white matter integrity. If patients claim that their performance is worsening or if they ask about the effects of DM on functioning, screening and assessment are recommended.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
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• v.35 no.4
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• pp.311-321
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• 2022

The report reviews recent research efforts in demonstrating a computing system whose operation principle mimics the dynamics of biological neurons. The temporal variation of the membrane potential of neurons is one of the key features that contribute to the information processing in the brain. We first summarize the neuron models that explain the experimentally observed change in the membrane potential. The function of ion channels is briefly introduced to understand such change from the molecular viewpoint. Dedicated circuits that can simulate the neuronal dynamics have been developed to reproduce the charging and discharging dynamics of neurons depending on the input ionic current from presynaptic neurons. Key elements include volatile memristors that can undergo volatile resistance switching depending on the voltage bias. This behavior called the threshold switching has been utilized to reproduce the spikes observed in the biological neurons. Various types of threshold switch have been applied in a different configuration in the hardware demonstration of neurons. Recent studies revealed that the memristor-based circuits could provide energy and space efficient options for the demonstration of neurons using the innate physical properties of materials compared to the options demonstrated with the conventional complementary metal-oxide-semiconductors (CMOS).

• 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.

• Journal of Genetic Medicine
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• v.21 no.1
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• pp.36-40
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• 2024

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome is a maternally inherited mitochondrial disorder that usually affects the cerebral cortex and prevents high-energy demands from being met. Herein, we present the case of a male patient who rapidly developed multiple seizures, headaches, and altered mentality accompanied by severe metabolic acidosis and lactic acidosis. Initially, a brain imaging study confirmed stroke-like lesions (SLLs) only in the cerebellum. During follow-up, newly developed SLLs with lactic acidosis were observed in the basal ganglia (BG), cerebellum, and occipital lobe. The m.3243A>G variant had been found in the patient and MELAS was diagnosed, despite the BG and cerebellum being atypical locations for SLLs in MELAS. Since most cases of m.3243A>G variant MELAS show SLLs in the cerebral cortex, this case is unusual considering the location of the lesion. We emphasize that in the case of lactic acidosis accompanied by neurological symptoms, such as seizures, as in this case, MELAS should be included in the differential diagnosis, even if SLLs are observed in areas other than the cerebral cortex.

• Korean Journal of Food Science and Technology
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• v.52 no.1
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• pp.60-66
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• 2020

This study examined the antioxidant activity and neuroprotective effects of ethanol extracts obtained from Diospyros kaki core (DCE). The total polyphenol and flavonoid contents in DCE was 786.47±15.27 and 31.14±0.82 mg/g, respectively. In addition, DCE exhibited a dose-dependent induction of radical scavenging activity, determined by 1,1-diphenyl-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonicacid) (ABTS), ferric reducing antioxidant power (FRAP), and reducing power assays. The viability of HT22 hippocampal cells was examined to investigate the neuroprotective effect of DCE. DCE treatment did not induce cytotoxicity at concentrations below 1,000 ㎍/mL. Additionally, DCE treatment in the background of H₂O₂ induce oxidative stress revealed a significant increase in the survival rat, indicated by increased SOD activity and decreased levels of MDA, a lipid peroxidation product. Therefore, the results suggest that DCE can be used as a source of natural antioxidants source and a therapeutic agent for the treatment of brain disorders induced by oxidative stress and neuronal damage.

• Progress in Medical Physics
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• v.27 no.2
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• pp.79-85
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• 2016

The objective of this study is to increase the accuracy of dose transmission in radiation therapy using two types of treatment tables, standard exact couch (Varian 21EX, Varian Medical Systems, Milpitas, CA) and 6D robotic couch (Novalis, BrainLAB A.G., Heimstetten, Germany)). We examined the dose attenuation based on the two types of treatment tables and studied the dose of attenuation using the phase (In/Out) for the standard exact couch. We measured the relative dose according to the incident angle of a penetrative photon beam under a treatment table. The incident angle of the photon beam was from $0^{\circ}$ to $360^{\circ}$ in the increments of $5^{\circ}$. The reference angle was set to $0^{\circ}$. Furthermore, the relative dose of the 6D robotic couch was measured using 6 MV and 15 MV, and that of the standard exact couch was measured at the sliding rail position (In-Out) using 6 MV and 10 MV. In the case of the standard exact couch, the measured relative dose was 16.53% (rails at the "In position," $175^{\circ}$, 6 MV), 12.42% (rails at the "In position," $175^{\circ}$, 10 MV), 13.13% (rails at the "Out position," $175^{\circ}$, 6 MV), and 9.96% (rails at the "Out position," $175^{\circ}$, 10 MV). In the case of the 6D robotic couch, the measured relative dose was 6.82% ($130^{\circ}$, 6 MV) and 4.92% ($130^{\circ}$, 15 MV). The photon energies were surveyed at the same incident angle. The dose attenuation for an energy of 10 MV was 4~5% lower than that for 6 MV. This indicated that the higher photon energy, lesser is the attenuation. The results of this study indicated that the attenuation rate for the 6D robotic couch was confirmed to be 1% larger than that for the standard exact couch at 6 MV and $180^{\circ}$. In the case of the standard exact couch, the dose attenuation was found to change rapidly in accordance with the phase ("In position" and "Out position") of the sliding rail.

• Journal of Biomedical Engineering Research
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• v.30 no.5
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• pp.401-411
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• 2009

In this paper, we correct pulse wave velocity(PWV) with heart-rate and derive regression equations to estimate intima-media thickness(IMT). Widely used methods for diagnosis of arteriosclerosis are IMT and PWV. Arterial wall stiffness determines the degree of energy absorbed by the elastic aorta and its recoil in diastole but there is not correlation between sclerosis and IMT in an existing study. In this study, we will correct PWV with heart-rate and get regression equation to estimate IMT using heart-rate correction index(HCI). We executed experiments for this study. Made up question of physical condition and measured electrocardiogram(ECG), photoplethysmogram (PPG) of finger-tip and toe-tip and ultrasound image of carotid artery. Calculated PWV and IMT using ECG, PPG and ultrasound image. We found that every p-value between PWV and IMT is not significant(<0.05). But p-value between IMT and HCI which is a corrected PWV using heart-rate is significant(>0.01). We use HCI and various measured parameter for estimating regression equation and apply backward estimation to select parameters for regression analysis. Result of backward estimation, found that only HCI is possible to derive proper regression equation of IMT. Relationship between PWV and IMT is the second order. Result of regression equation of E-H PWV is $R^2$=0.735, adj $R^2$=0.711. This is the best correlation value. We calculate error of its analysis for verification of earlobe PWV regression equation. Its result is RMSEP=0.0328, MAPE(%) = 4.7622. Like this regression analysis, we know that HCI is useful parameter and relationship between PWV, HCI and IMT. In addition, we are able to suggest possibility which is that we can get different parameter of prediction throughout just one measurement.

• Development and Reproduction
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• v.15 no.3
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• pp.249-256
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• 2011

Nesfatin-1/NUCB2, which is secreted from the brain, is known to control appetite and energy metabolism. Recent studies have been shown that nesfatin-1/NUCB2 was expressed not only in the brain, but it was also expressed in the gastric organs and adipose tissue. However, little is known about the expression of nesfatin-1/NUCB2 in the male reproductive system. Therefore, we examined whether the nesfatin-1/NUCB2 and its binding site exists in the male reproductive organs. Nesfatin-1/NUCB2 mRNA and protein were detected in the mouse testis and epididymis by PCR and Western blot analysis. As a result of the immunohistochemistry staining, the nesfatin-1 protein was localized at the interstitial cells and Leydig cells in the testis. Nesfatin-1 binding sites were also displayed at boundary cells in the tunica albuginea. Furthermore, in order to examine if the expression of nesfatin-1/NUCB2 mRNA in the testis and epididymis were affected by gonadotropin, its mRNA expression was analyzed after PMSG administration into mice. NUCB2 mRNA expression levels were increased in both of the testis and epididymis after PMSG administration. These results demonstrated for the first time that nesfatin-1 and its binding site were expressed in the mouse testis and epididymis. In addition, nesfatin-1/NUCB2 mRNA expression was controlled by gonadotropin, suggesting a possible role of nesfatin-1 in the male reproductive organs as a local regulator. Due to this, further study is needed to elucidate the functions of nesfatin-1 on the male reproductive system.

• Journal of Nutrition and Health
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• v.28 no.5
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• pp.375-386
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• 1995

This study was designed to investigate the changes in energy substrates, glucose and non-esterified fatty acid(NEFA), and fatty acid compositions in serum, following physiolgical stress in rats fed diets containing various fatty acids. Forty two Sprague-Dawley strain male rats, weighing 108$\pm$2.1g, were fed 3 different experimental diets for 4 weeks. The diets were composed of 105 fat(w/w) of either corn oil(CO;18:2 n6:57%), plant perilla oil(PO;18:3 n3:59%), or tuna fish oil(FO;20:5 n3:17%%, 22:6 n3:19%). After 4 weeks of feeding, each group wa subdiveided into (a) control, (b) 2 min swim in ice-cold water. Animals wer decapitated 20min after commencing the swim; trunk blood, brain, liver and epididymal fat pad were obtained. The levels of serum corticosterone, glucose, NEFA, triglyceride, fatty acid compositions, brain serotonin and 5-hydroxyindoleacetic acid were determined. Basal levels of corticosterone na NEFA of serum were significantly lower in fish oil fed animals than those of any other oil fed animals. Compared to either perilla oil-fed or corn oil-fed rats, cold swim stress in fish oil fed rats produced significantly smaller NEFA and larger corticosterone responses. However, there was no significant difference in basal levels of serum glucose. Stress increased serum glucose levels slightly, and the amount of increment was larger in fish oil rats than those of any other oil fed rats than those of any other oil fed rats, although all the values were normal level. Dietary fats and stress did not affect serotonin metabolism. In additions, the composition of fatty acids in serum was significantly affected by the dietary compostion of fatty acids and stress. Stress induced decreases in monounsaturated fatty acid and non-polyunsaturated fatty acid concentration in either perilla oil fed or fish group, but did not in corn oil fed group. Stress resulted in changes in fatty acid metabolism similar to that associated with essential fatty acid(EFA) dificiency, when feeding animals n-3 fatty acids in diet. In conclusion, feeding fish oil was more effective to decrease NEFA in serum than feeding perilla oil or corn oil and improved lipid metabolism, when the rats were maintained in normal or exposed to stressful environment. However, the fact that feeding diet containing n-3 fatty acids decreased EFA status under stress suggests that the requirement of n-6 PUFA should be increased in these groups.