• Biomolecules & Therapeutics
• /
• v.20 no.2
• /
• pp.152-157
• /
• 2012

Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the brain and a structural component of neuronal membranes. Changes in DHA content of neuronal membranes lead to functional changes in the activity of receptors and other proteins which might be associated with synaptic function. Accumulating evidence suggests the beneficial effects of dietary DHA supplementation on neurotransmission. This article reviews the beneficial effects of DHA on the brain; uptake, incorporation and release of DHA at synapses, effects of DHA on synapses, effects of DHA on neurotransmitters, DHA metabolites, and changes in DHA with age. Further studies to better understand the metabolome of DHA could result in more effective use of this molecule for treatment of neurodegenerative or neuropsychiatric diseases.

• Animal cells and systems
• /
• v.4 no.3
• /
• pp.215-221
• /
• 2000

Our anatomical and behavioral studies of embryonic rats that developed in microgravity suggest that the vestibular sensory system, like the visual system, has genetically mediated precesses of development that establish crude connections between the periphery and the brain. Environmental stimuli also regulate connection formation including terminal branch formation and fine-tuning of synaptic contacts. Axons of vestibular sensory neurons from grabistatic as well as linear acceleration receptors reach their targets in both microgravity and norm81 gravity, suggesting that this is a genetically regulated component of development. However, microgravity exposure delays the development of terminal branches and synapses in gravistatic but not linear acceleration-sensitive neurons and also produces behavioral changes. These latter changes reflect environmentally controlled processes of development.

• Journal of Biomedical Engineering Research
• /
• v.28 no.1
• /
• pp.17-23
• /
• 2007

Long-term potentiation (LTP) of synaptic transmission is the most widely studied model for learning and memory. However its mechanisms are not clearly elucidated and are a subject for intense investigation. Previous attempts to decipher cellular mechanisms and network properties involved a current-source density analysis (CSDA) of the LTP from small animal hippocampus measured with a limited number of microelectrodes (typically <3), only revealing limited nature of spatiotemporal dynamics. Recent advancement in multi-electrode array (MEA) technology allows continuous and simultaneous recordings of LTP with more than 60 electrodes. However CSDA via the standard Laplacian transform is still limited due to its relatively high sensitivity toward noise, inability of resolving overlapped current sources and sinks, and its requirement for tissue conductivity values. In this study, we propose a new methodology for improved CSDA. Independent component analysis and its joint use (i.e., Joint-ICA) are applied to extract spatiotemporal components of LTP. The results show that ICA and Joint-ICA are capable of extracting independent spatiotemporal components of LTP generators. The ICs of LTP indicate the reversing roles of current sources and sinks which are associated with LTP.

• BMB Reports
• /
• v.40 no.3
• /
• pp.302-314
• /
• 2007

N type calcium channels (CaV2.2) play a key role in the gating of transmitter release at presynaptic nerve terminals. These channels are generally regarded as parts of a multimolecular complex that can modulate their open probability and ensure their location near the vesicle docking and fusion sites. However, the proteins that comprise this component remain poorly characterized. We have carried out the first open screen of presynaptic CaV2.2 complex members by an antibody-mediated capture of the channel from purified rat brain synaptosome lysate followed by mass spectroscopy. 589 unique peptides resulted in a high confidence match of 104 total proteins and 40 synaptosome proteome proteins. This screen identified several known CaV2.2 interacting proteins including syntaxin 1, VAMP, protein phosphatase 2A, $G_{o\alpha}$, G$\beta$ and spectrin and also a number of novel proteins, including clathrin, adaptin, dynamin, dynein, NSF and actin. The unexpected proteins were classified within a number of functional classes that include exocytosis, endocytosis, cytoplasmic matrix, modulators, chaperones, and cell-signaling molecules and this list was contrasted to previous reports that catalogue the synaptosome proteome. The failure to detect any postsynaptic density proteins suggests that the channel itself does not exhibit stable trans-synaptic attachments. Our results suggest that the channel is anchored to a cytoplasmic matrix related to the previously described particle web.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.194-199
• /
• 2002

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

• Molecules and Cells
• /
• v.42 no.1
• /
• pp.36-44
• /
• 2019

Alzheimer's disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. ${\beta}-Amyloid$ ($A{\beta}$) peptide is the predominant proteinaceous component of senile plaques. The amyloid hypothesis states that $A{\beta}$ initiates the cascade of events that result in AD. Amyloid precursor protein (APP) processing plays an important role in $A{\beta}$ production, which initiates synaptic and neuronal damage. ${\delta}-Catenin$ is known to be bound to presenilin-1 (PS-1), which is the main component of the ${\gamma}-secretase$ complex that regulates APP cleavage. Because PS-1 interacts with both APP and ${\delta}-catenin$, it is worth studying their interactive mechanism and/or effects on each other. Our immunoprecipitation data showed that there was no physical association between ${\delta}-catenin$ and APP. However, we observed that ${\delta}-catenin$ could reduce the binding between PS-1 and APP, thus decreasing the PS-1 mediated APP processing activity. Furthermore, ${\delta}-catenin$ reduced PS-1-mediated stabilization of APP. The results suggest that ${\delta}-catenin$ can influence the APP processing and its level by interacting with PS-1, which may eventually play a protective role in the degeneration of an Alzheimer's disease patient.

• Journal of the Korean Institute of Intelligent Systems
• /
• v.16 no.2
• /
• pp.179-184
• /
• 2006

An intuitive understanding of the dynamic pattern generation in asymmetric networks may be considered an essential component in developing models for the dynamic information processing. It has been reported that the neural network with cyclic connections generates multiple limit cycles. The dynamics of discrete time network with cyclic connections has been investigated intensively. However, the dynamics of a cyclic connection neural network in continuous-time has not been well-known due to the considerable complexity involved in its calculation. In this paper, the dynamic behavior of a continuous-time cyclic connection neural network, in which each neuron is connected only to its nearest neurons with binary synaptic weights of ${\pm}1$, has been investigated. Furthermore, the dynamics and stability of the network have been analyzed using a piece-wise linear approximation.

• Progress in Medical Physics
• /
• v.19 no.3
• /
• pp.157-163
• /
• 2008

Retinal prosthesis is regarded as the most feasible method for the blind caused by retinal diseases such as retinitis pigmentosa or age-related macular degeneration. One of the prerequisites for the success of retinal prosthesis is the optimization of the electrical stimuli applied through the prosthesis. Since electrical characteristics of degenerate retina are expected to differ from those of normal retina, we investigated differences of the retinal waveforms in normal and degenerate retina to provide a guideline for the optimization of electrical stimulation for the upcoming prosthesis. After isolation of retina, retinal patch was attached with the ganglion cell side facing the surface of microelectrode arrays (MEA). $8{\times}8$ grid layout MEA (electrode diameter: $30{\mu}m$, electrode spacing: $200{\mu}m$, and impedance: 50 $k{\Omega}$ at 1 kHz) was used to record in-vitro retinal ganglion cell activity. In normal mice (C57BL/6J strain) of postnatal day 28, only short duration (<2 ms) retinal spikes were recorded. In rd/rd mice (C3H/HeJ strain), besides normal spikes, waveform with longer duration (~100 ms), the slow wave component was recorded. We attempted to understand the mechanism of this slow wave component in degenerate retina using various synaptic blockers. We suggest that stronger glutamatergic input from bipolar cell to the ganglion cell in rd/rd mouse than normal mouse contributes the most to this slow wave component. Out of many degenerative changes, we favor elimination of the inhibitory horizontal input to bipolar cells as a main contributor for a relatively stronger input from bipolar cell to ganglion cell in rd/rd mouse.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.3
• /
• pp.219-228
• /
• 2015

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.