• Korean Journal of Biological Psychiatry
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• v.18 no.4
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• pp.169-175
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• 2011

Stress, a risk factor of major depression induces cytokine mediated inflammation and decreased neurogenesis. In patients with major depression, significant increases of pro-inflammatory cytokines have been consistently reported. The pro-inflammatory cytokines can stimulate the hypothalamic-pituitary-adrenal (HPA) axis to release glucocorticoids. In the brain, microglia and play a role of immune activation in response to stress. Increased pro-inflammatory cytokine play a role in restricting neurogenesis in the brain. Although neurogenesis may not be essential for the development of depression, it may be required for clinically effective antidepressant treatment. Hence, stimulation of neurogenesis is regarded as a promising strategy for new antidepressant targets. This review introduces changes in neurotransmitter, cytokine and neurogenesis in major depression and explores the possible relationship between pro-inflammatory cytokines and neurogenesis related to stress in major depression.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.32-32
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• 2003

In the neuron, SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) assembly plays a central role in driving membrane fusion, a required process for neurotransmitter release. In the cytoplasm, vesicular SNARE VAMP2 (vesicle-associated membrane protein 2) engages with two plasma membrane SNAREs syntaxin 1A and SNAP-25 (synaptosome-associated protein of 25 kDa) to form the core complex that bridges two membranes. While various factors regulate SNARE assembly, the membrane also plays the regulatory role by trapping VAMP2 in the membrane. The fluorescence and EPR analyses revealed that the insertion of seven C-terminal core-forming residues into the membrane controls complex formation of the entire core region, even though preceding 54 core-forming residues are fully exposed and freely moving. When two interfacial Trp residues in this region were replaced with hydrophilic serine residues, the mutation supported rapid complex formation.

• Kidney Research and Clinical Practice
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• v.37 no.4
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• pp.315-322
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• 2018

The high mortality rates associated with acute kidney injury are mainly due to extra-renal complications that occur following distant-organ involvement. Damage to these organs, which is commonly referred to as multiple organ dysfunction syndrome, has more severe and persistent effects. The brain and its sub-structures, such as the hippocampus, are vulnerable organs that can be adversely affected. Acute kidney injury may be associated with numerous brain and hippocampal complications, as it may alter the permeability of the blood-brain barrier. Although the pathogenesis of acute uremic encephalopathy is poorly understood, some of the underlying mechanisms that may contribute to hippocampal involvement include the release of multiple inflammatory mediators that coincide with hippocampus inflammation and cytotoxicity, neurotransmitter derangement, transcriptional dysregulation, and changes in the expression of apoptotic genes. Impairment of brain function, especially of a structure that has vital activity in learning and memory and is very sensitive to renal ischemic injury, can ultimately lead to cognitive and functional complications in patients with acute kidney injury. The objective of this review was to assess these complications in the brain following acute kidney injury, with a focus on the hippocampus as a critical region for learning and memory.

• BMB Reports
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• v.54 no.3
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• pp.149-156
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• 2021

The well-known second messenger cyclic adenosine monophosphate (cAMP) regulates the morphology and physiology of neurons and thus higher cognitive brain functions. The discovery of exchange protein activated by cAMP (Epac) as a guanine nucleotide exchange factor for Rap GTPases has shed light on protein kinase A (PKA)-independent functions of cAMP signaling in neural tissues. Studies of cAMP-Epac-mediated signaling in neurons under normal and disease conditions also revealed its diverse contributions to neurodevelopment, synaptic remodeling, and neurotransmitter release, as well as learning, memory, and emotion. In this mini-review, the various roles of Epac isoforms, including Epac1 and Epac2, highly expressed in neural tissues are summarized, and controversies or issues are highlighted that need to be resolved to uncover the critical functions of Epac in neural tissues and the potential for a new therapeutic target of mental disorders.

• Molecules and Cells
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• v.47 no.2
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• pp.100030.1-100030.14
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• 2024

Both brown and white adipose tissues (BAT/WAT) are innervated by the peripheral nervous system, including efferent sympathetic nerves that communicate from the brain/central nervous system out to the tissue, and afferent sensory nerves that communicate from the tissue back to the brain and locally release neuropeptides to the tissue upon stimulation. This bidirectional neural communication is important for energy balance and metabolic control, as well as maintaining adipose tissue health through processes like browning (development of metabolically healthy brown adipocytes in WAT), thermogenesis, lipolysis, and adipogenesis. Decades of sensory nerve denervation studies have demonstrated the particular importance of adipose sensory nerves for brown adipose tissue and WAT functions, but far less is known about the tissue's sensory innervation compared to the better-studied sympathetic nerves and their neurotransmitter norepinephrine. In this review, we cover what is known and not yet known about sensory nerve activities in adipose, focusing on their effector neuropeptide actions in the tissue.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.756-763
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• 2002

We have previously demonstrated that repeated injections of nicotine produced an increase in locomotor activity, dopamine(DA), release and c-Fos expression in the nucleus accumbens, one of the major projection areas of the central DA system. Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. And many studies have shown that Coptidis Rhizoma has a suppressive effect on the central nervous system (CNS) and can affect the neurotransmitter systems in the CNS. In order to investigate whether acupuncture and Coptidis Rhizoma have an influence on nicotine-induced reinforcing and behavioral effects, we examined the effect of zusanli(ST36) and Coptidis Rhizoma on repeated nicotine-induced locomotor activity, and zusanli(ST36) on c-Fos expression as an important maker of postsynaptic neuronal activity in nucleus accumbens. Male SD rats received Coptidis Rhizoma (100mg/kg, p.o.) 30 min before injections of nicotine (0.4 mg/kg, s.c.) for 7 days. Rats were followed withdrawal for 3 days and one challenge for 1 day. Systemic challenge with nicotine produced a much larger increase in locomotor activity. Pretreatment with acupuncture at zusanli(ST36, 100Hz) and Coptidis Rhizoma decreased in nicotine-induced locomotor activity. These results demonstrated that reduction in locomotor activity by acupuncture at zusanli(ST36, 100Hz) and Coptidis Rhizoma may be mediated by reduction of dopamine release. Our results suggest that acupuncture at zusanli(ST36, 100Hz) and Coptidis Rhizoma may have therapeutic effect on nicotine addiction.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.161-170
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• 2004

Molecular Nuclear Neuro-Imaging in "CNS" drug discovery and development tan be divided into four categories that are clearly inter-related.(1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and "CNS fingerprinting" the neuroanatomy of drug effects;(4) Functional mapping to examing disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering, might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy.

• Applied Biological Chemistry
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• v.51 no.1
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• pp.79-83
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• 2008

The present study describes glutamate which is known as excitatory neurotransmitter is related with oxidative damages and the Viola mandshurica extracts. Showed protective effects against glutamate-induced cytotoxicity. The protective effect of antioxidant on the glutamate treated N18-RE-I05 cells was determined by a MTT reduction assay. The neuroprotective effect of methanol, ethanol, and acetone extracts from V. mandshurica against glutamate-induced cytotoxicity was assessed by the results of an MTT reduction assay. Among the three extracts, the acetone extract showed the highest protective effect by the results of an lactate dehydrogenase release assay. Therefore, these results suggest that V. mandshurica extracts could be a new potential candidate against glutamate-induced oxidative stress.

• BMB Reports
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• v.48 no.5
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• pp.249-255
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• 2015

PTPRT/RPTPρ is the most recently isolated member of the type IIB receptor-type protein tyrosine phosphatase family and its expression is restricted to the nervous system. PTPRT plays a critical role in regulation of synaptic formation and neuronal development. When PTPRT was overexpressed in hippocampal neurons, synaptic formation and dendritic arborization were induced. On the other hand, knockdown of PTPRT decreased neuronal transmission and attenuated neuronal development. PTPRT strengthened neuronal synapses by forming homophilic trans dimers with each other and heterophilic cis complexes with neuronal adhesion molecules. Fyn tyrosine kinase regulated PTPRT activity through phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT. Phosphorylation induced homophilic cis dimerization of PTPRT and resulted in the inhibition of phosphatase activity. BCR-Rac1 GAP and Syntaxin-binding protein were found as new endogenous substrates of PTPRT in rat brain. PTPRT induced polymerization of actin cytoskeleton that determined the morphologies of dendrites and spines by inhibiting BCR-Rac1 GAP activity. Additionally, PTPRT appeared to regulate neurotransmitter release through reinforcement of interactions between Syntaxin-binding protein and Syntaxin, a SNARE protein. In conclusion, PTPRT regulates synaptic function and neuronal development through interactions with neuronal adhesion molecules and the dephosphorylation of synaptic molecules. [BMB Reports 2015; 48(5): 249-255]

• Animal cells and systems
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• v.11 no.2
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• pp.199-204
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• 2007

HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, whose gene family consists of four subunits (HCN1-4), mediate depolarizing cation currents and contribute to controlling neuronal excitability. In the present study, immunohistochemical and electrophysiological approaches were used to elucidate the role of HCN channels in the cerebellum. Immunohistochemical labeling for HCN1 and HCN2 channels revealed localized expression of both channels at pinceau, the specialized structure of presynaptic axon terminals of basket cells. To determine the functional role of the presynaptic HCN channels, spontaneous inhibitory postsynaptic currents (IPSCs) were recorded from Purkinje cells, the main synaptic targets of basket cells in the cerebellum. While activation of HCN channels by 8-bromo-cAMP increased amplitude of spontaneous IPSCs, blockade of the activated HCN channels by subsequent ZD7288 application reduced the amplitude of spontaneous IPSCs to the level far below the control. Our results imply that modulation of HCN1 and HCN2 channels in presynaptic terminals of basket cells regulates neurotransmitter release, thereby controlling the excitability of Purkinje cells.