• The Korean Journal of Physiology and Pharmacology
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• 제18권2호
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• pp.135-141
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• 2014

The downregulation of A-type $K^+$ channels ($I_A$ channels) accompanying enhanced somatic excitability can mediate epileptogenic conditions in mammalian central nervous system. As $I_A$ channels are dominantly targeted by dendritic and postsynaptic processings during synaptic plasticity, it is presumable that they may act as cellular linkers between synaptic responses and somatic processings under various excitable conditions. In the present study, we electrophysiologically tested if the downregulation of somatic $I_A$ channels was sensitive to synaptic activities in young hippocampal neurons. In primarily cultured hippocampal neurons (DIV 6~9), the peak of $I_A$ recorded by a whole-cell patch was significantly reduced by high KCl or exogenous glutamate treatment to enhance synaptic activities. However, the pretreatment of MK801 to block synaptic NMDA receptors abolished the glutamate-induced reduction of the $I_A$ peak, indicating the necessity of synaptic activation for the reduction of somatic $I_A$. This was again confirmed by glycine treatment, showing a significant reduction of the somatic $I_A$ peak. Additionally, the gating property of $I_A$ channels was also sensitive to the activation of synaptic NMDA receptors, showing the hyperpolarizing shift in inactivation kinetics. These results suggest that synaptic LTP possibly potentiates somatic excitability via downregulating $I_A$ channels in expression and gating kinetics. The consequential changes of somatic excitability following the activity-dependent modulation of synaptic responses may be a series of processings for neuronal functions to determine outputs in memory mechanisms or pathogenic conditions.

• Toxicological Research
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• 제30권4호
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• pp.235-242
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• 2014

Cancer cells are known to drastically alter cellular energy metabolism. The Warburg effect has been known for over 80 years as pertaining cancer-specific aerobic glycolysis. As underlying molecular mechanisms are elucidated so that cancer cells alter the cellular energy metabolism for their advantage, the significance of the modulation of metabolic profiles is gaining attention. Now, metabolic reprogramming is becoming an emerging hallmark of cancer. Therapeutic agents that target cancer energy metabolism are under intensive investigation, but these investigations are mostly focused on the cytosolic glycolytic processes. Although mitochondrial oxidative phosphorylation is an integral part of cellular energy metabolism, until recently, it has been regarded as an auxiliary to cytosolic glycolytic processes in cancer energy metabolism. In this review, we will discuss the importance of mitochondrial respiration in the metabolic reprogramming of cancer, in addition to discussing the justification for using mitochondrial DNA somatic mutation as metabolic determinants for cancer sensitivity in glucose limitation.

• Journal of Oral Medicine and Pain
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• 제38권4호
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• pp.333-338
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• 2013

Purpose: 특정한 형태의 이명은 그 발생에 있어서 청각계와 체성감각계의 상호작용이 핵심적인 역할을 하고 있음을 시사하는 증거들이 지속적으로 연구되어 발표되고 있다. 이러한 맥락에서 본 연구는 턱의 운동이 이명에 미치는 영향을 조사하고자 계획되었다. Methods: 163명 이명 환자의 217귀를 대상으로 순음청력검사, 이명의 특성에 대한 설문조사, 이명의 크기, 지속시간 및 괴로운 정도에 대한 시각사상척도(visual analogue scale) 조사와 함께 9 항목의 턱관절의 등척성 운동에 따른 이명의 크기 변화를 조사하는 이명의 체성조절 검사를 시행하였다. Results: 체성조절 검사를 시행한 이명 환자의 217귀 중 125귀(57.6 %)에서 이명의 크기가 변함을 관찰할 수 있었다. 일측성 이명 109귀중 70귀(64.2%)에서 체성조절에 반응하여 양측성 이명 108귀중 55귀(50.9%)의 반응보다 유의하게 높은 빈도를 보였다(p<0.05). 검사 항목 모두에서 이명의 크기 증가가 감소보다 더 자주 관찰되었고, 크기 증가의 빈도는 6.7-15.4%로 개구 및 이악물기 항목에서 가장 자주 이명의 크기 증가가 유발되었다. Conclusion: 본 연구 결과, 턱의 운동은 이명을 악화 혹은 유발시킬 수 있으며, 체성조절 검사는 턱 관절의 자극이 이명의 유발 및 악화요인 인가를 평가하는 방법으로 활용할 수 있을 것으로 생각된다.

• 한국유기농업학회지
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• 제12권2호
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• pp.231-241
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• 2004

In recent years, many researches are actively undertaken for environmental-friendly animal production according to the increased understanding about food safety because of the outbreak of various diseases such as mad cow disease, Foot and mouth disease and Poultry Influenza virus. However, high quality(higher safety)- animal production may not be successful without increasing of disease resistance of animal and the improvement of feeding environment. To increase the disease resistance is able to be accomplished by stimulating the immune function. The present study was undertaken to investigate the effects of enzyme mixture reinforced with ${\beta}$-glucanase activity which degrade polysaccharide to release ${\beta}$-glucan known as stimulator of immune function on the change of milk production and somatic cell count. After 12weeks of experimental feeding, milk production tended to be increased and somatic cell count was decreased from average $227{\times}10^4$ to $37.1{\times}10^4$. Milk protein and solid-fat content were tended to increase but milk fat showed decreasing tendency by the feeding of enzyme mixture. All together, it has been suggest6d that the improvement of high quality milk production may be possible through the dietary addition of immune modulating enzyme mixture in lactating dairy cows.

• International Journal of Stem Cells
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• 제16권1호
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• pp.27-35
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• 2023

Background and Objectives: Spermatogonial stem cells (SSCs) are the most primitive cells in spermatogenesis and are the only adult stem cells capable of passing on the genome of a given species to the next generation. SSCs are the only adult stem cells known to exhibit high Oct4 expression and can be induced to self-reprogram into pluripotent cells depending on culture conditions. Epigenetic modulation is well known to be involved in the induction of pluripotency of somatic cells. However, epigenetic modulation in self-reprogramming of SSCs into pluripotent cells has not been studied. Methods and Results: In this study, we examined the involvement of epigenetic modulation by assessing whether selfreprogramming of SSCs is enhanced by treatment with epigenetic modulators. We found that second-generation selective class I HDAC inhibitors increased SSC reprogramming efficiency, whereas non-selective HDAC inhibitors had no effect. Conclusions: We showed that pluripotent stem cells derived from adult SSCs by treatment with small molecules with epigenetic modulator functions exhibit pluripotency in vitro and in vivo. Our results suggest that the mechanism of SSC reprogramming by epigenetic modulator can be used for important applications in epigenetic reprogramming research.

• Journal of Oral Medicine and Pain
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• 제40권3호
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• pp.89-95
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• 2015

All living organisms have a biological clock that orchestrates every biological process and function, and this internal clock operates following a circadian rhythm. This biological clock is known to influence various clinical indicators such as blood pressure and body temperature. Also, the fluctuation of signs and symptoms of diseases including pain disorders are affected by circadian rhythm. It has been reported that the pain intensity of various somatic and neuropathic pain disorders show unique pain patterns that depend on the passage of time. The generation of pain patterns could be explained by extrinsic (e.g., physical activity, tactile stimulation, ambient temperature) and also intrinsic factors (neural and neuroendocrine modulation) that are related to the circadian rhythm. It is important to recognize and identify the individual pain pattern in pain therapy to approve treatment outcome. Moreover, chronotherapeutics which considers pain patterns and pharmacokinetics in context of the circadian rhythm could produce greater analgesia in response to medication. However, only a limited number of studies handle the issue of pain patterns according to circadian rhythm and chronotherapeutics in the orofacial region. The present review intends to reflect on the most recent and relevant data concerning the bidirectional relation between pain disorders of the orofacial region and circadian patterns.

• International Journal of Oral Biology
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• 제31권4호
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• pp.113-118
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• 2006

In the primary sensory neuron of the mesencephalic trigeminal nucleus (MTN), the peripheral axon supplies a large number of annulospiral endings surrounding intrafusal fibers encapsulated in single muscle spindles while the central axon sends only a few number of synapses onto single ${\alpha}-motoneurons({\alpha}-MNs)$. Therefore, the ${\alpha}-{\gamma}$ linkage is thought to be very crucial in the jaw-closing movement. Spike activity in a ${\gamma}-motoneuron\;({\gamma}-MN)$ would induce a large number of impulses in single peripheral axons by activating many intrafusal fibers simultaneously, subsequently causing an activation of ${\alpha}-MNs$ in spite of the small number of synapses. Thus, the activity of ${\gamma}-MNs$ may be vital for modulation of jaw-closing movements. Independently of such a spindle activity modulated by ${\gamma}-MNs$, somatic depolarization in MTN neurons is known to trigger the oscillatory spike activity. Nevertheless, the trafficking of these spikes arising from the two distinct sources of MTN neurons is not well understood. In this short review, switching among multiple functional modes of MTN neurons is discussed. Subsequently, it will be discussed which mode can support the ${\alpha}-{\gamma}$ linkage. In our most recent study, simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-back-propagation from the spike-initiation site in the stem axon to the soma in response to a somatic current pulse. The persistent $Na^+$ current was found to be responsible for the spike-initiation in the stem axon, the activation threshold of which was lower than those of soma spikes. Somatic inputs or impulses arising from the sensory ending, whichever trigger spikes in the stem axon first, would be forwarded through the central axon to the target synapse. We also demonstrated that at hyperpolarized membrane potentials, 4-AP-sensitive $K^+$ current ($IK_{4-AP}$) exerts two opposing effects on spikes depending on their origins; the suppression of spike initiation by increasing the apparent electrotonic distance between the soma and the spike-initiation site, and the facilitation of axonal spike invasion at higher frequencies by decreasing the spike duration and the refractory period. Through this mechanism, the spindle activity caused by ${\gamma}-MNs$ would be safely forwarded to ${\alpha}-MNs$. Thus, soma spikes shaped differentially by this $IK_{4-AP}$ depending on their origins would reflect which one of the two inputs was forwarded to the target synapses.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.37-43
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• 1993

Electrical or chemical stimulation of many areas in the brainstem modulates activity of dorsal horn neurons (DHN). This is known to be mediated by a population of bulbospinal neurons. Yet, little is known about responses of DHNs to stimulation of the caudal ventrolateral medulla (CVLM). Thus, the purpose of the present study is to see if there is any change in activity of DHNs when CVLM is stimulated electrically. Thirty-one DHNs were recorded from dorsal horn of the spinal cord. Fourteen DHNs (45%) were classified as wide dynamic range neurons and 9 (19%) were high threshold cells, and 4 (13%) and 4 (13%) were deep and low threshold neurons, respectively. Among 31 neurons tested for responses to stimulation of CVLM, 21 DHNs (68%) were inhibited by the electrical stimulation of CVLM ($200{\mu}A,\;100{\mu}s$ duration, 100 Hz), and 9 cells (39%) did not show any change in neuronal activity. One neuron was excited by the stimulation. The electrical stimulation of CVLM not only inhibited spontaneous activity of DHNs but also inhibited evoked responses of DHNs to somatic stimulation in the receptive field. These data suggest that CVLM is one of the pain-modulatory areas that control transmission of ascending information of noxious input to the brain from the spinal cord.

• The Korean Journal of Physiology
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• 제28권1호
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• pp.99-103
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• 1994

Single neuronal activities were recorded in the cuneate nucleus of awake rats during rest and running behavior. Movement-induced changes in somatic sensory transmission were tested by generating post-stimulus time histograms of these neurons' responses to stimulation through eleetrodes chronically implanted under the skin of the forepaw, during control resting behavior and during two standardized speeds of locomotor movement: slow (1.0 steps/s), fast (2.0 steps/s). The magnitudes of firing during these responses were measured and normalized as percentage increases over background firing. The averaged evoked unit responses were facilitated by $+59.3{\pm}12.5%\;and\;+25.6{\pm}5.4%$ (SEM) as compared with resting behavior, during slow and fast movement respectively. This is to be compared with the movement-induced sensory suppressions observed previously in the ventrobasal thalamus $(-31.0%{\pm}1.9%)$ and in the primary somatosensory cortex $(-71.2%{\pm}3.8%)$ of slowly running rats. These results suggest that afferent somatosensory information may be uniquely modulated at each sensory relay, such that it may be facilitated at brainstem level and then subjected to suppression at higher somatosensory nuclei during movement.

• The Korean Journal of Pain
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• 제37권2호
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• pp.107-118
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• 2024

Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.