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Capsaicin Blocks the Hyperpolarization-Activated Inward Currents via TRPV1 in the Rat Dorsal Root Ganglion Neurons.

Experimental Neurobiology.2012;21(2):75-82. doi:10.5607/en.2012.21.2.75

Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, prolonged exposures of capsaicin will cause desensitization to nociceptive stimuli. Hyperpolarization-activated cation currents (Ih) contribute to the maintenance of the resting membrane potential and excitability of neurons. In the cultured dorsal root ganglion (DRG) neurons, we investigated mechanisms underlying capsaicin-mediated modulation of Ih using patch clamp recordings. Capsaicin (1 microM) inhibited Ih only in the capsaicin-sensitive neurons. The capsaicin-induced inhibition of Ih was prevented by preexposing the TRPV1 antagonist, capsazepine (CPZ). Capsaicin-induced inhibition of Ih was dose dependent (IC50= 0.68 microM) and partially abolished by intracellular BAPTA and cyclosporin A, specific calcineurin inhibitor. In summary, the inhibitory effects of capsaicin on Ih are mediated by activation of TRPV1 and Ca(2+)-triggered cellular responses. Analgesic effects of capsaicin have been thought to be related to desensitization of nociceptive neurons due to depletion of pain-related substances. In addition, capsaicin-induced inhibition of Ih is likely to be important in understanding the analgesic mechanism of capsaicin.
Animals ; Calcineurin ; Capsaicin ; Cyclosporine ; Egtazic Acid ; Ganglia, Spinal ; Inflammation ; Membrane Potentials ; Neurons ; Nociceptors ; Rats ; Spinal Nerve Roots

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Neurochemical Properties of Dental Primary Afferent Neurons.

Hue VANG ; Gehoon CHUNG ; Hyun Yeong KIM ; Seok Beom PARK ; Sung Jun JUNG ; Joong Soo KIM ; Seog Bae OH

Experimental Neurobiology.2012;21(2):68-74. doi:10.5607/en.2012.21.2.68

The long belief that dental primary afferent (DPA) neurons are entirely composed of nociceptive neurons has been challenged by several anatomical and functional investigations. In order to characterize non-nociceptivepopulation among DPA neurons, retrograde transport fluorescent dye was placed in upper molars of rats and immunohistochemical detection of peripherin and neurofilament 200 in the labeled trigeminal ganglia was performed. As the results, majority ofDPA neurons were peripherin-expressing small-sized neurons, showing characteristic ofnociceptive C-fibers. However, 25.7% of DPA were stained with antibody against neurofilament 200, indicating significant portion of DPA neurons are related to large myelinated Abeta fibers. There were a small number of neurons thatexpressed both peripherin and neurofilament 200, suggestive of Adelta fibers. The possible transition of neurochemical properties by neuronal injury induced by retrograde labeling technique was ruled out by detection of minimal expression of neuronal injury marker, ATF-3. These results suggest that in addition to the large population of C-fiber-related nociceptive neurons, a subset of DPA neurons is myelinated large neurons, which is related to low-threshold mechanosensitive Abeta fibers. We suggest that these Abeta fiber-related neurons might play a role as mechanotransducers of fluid movement within dentinal tubules.
Animals ; Dentin ; Intermediate Filament Proteins ; Membrane Glycoproteins ; Molar ; Myelin Sheath ; Nerve Tissue Proteins ; Neurofilament Proteins ; Neurons ; Neurons, Afferent ; Nociceptors ; Rats ; Trigeminal Ganglion

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Differential Expressions of Synaptogenic Markers between Primary Cultured Cortical and Hippocampal Neurons.

Yun Gi KIM ; Young Il LEE

Experimental Neurobiology.2012;21(2):61-67. doi:10.5607/en.2012.21.2.61

Primary dissociated neuronal cultures are widely used research tools to investigate of pathological mechanisms and to treat various central and peripheral nervous system problems including trauma and degenerative neuronal diseases. We introduced a protocol that utilizes hippocampal and cortical neurons from embryonic day 17 or 18 mice. We applied appropriate markers (GAP-43 and synaptophysin) to investigate whether neurite outgrowth and synaptogenesis can be distinguished at a particular period of time. GAP-43 was found along the neural processes in a typical granular pattern, and its expression increased proportionally as neurites lengthened during the early in vitro period. Unlike GAP-43, granular immunoreactive patterns of synaptophysin along the neurites were clearly found from day 2 in vitro with relatively high immunoreactive levels. Expression of synaptic markers from cortical neurons reached peak level earlier than that of hippocampal neurons, although neurite outgrowths of hippocampal neurons were faster than those of cortical neurons. The amount of peak synaptic markers expressed was also higher in cortical neurons than that in hippocampal neurons. These results strongly suggest the usefulness of primary cultured neurons from mice embryos for synaptic function and plasticity studies, because of their clear and typical patterns of morphology that establish synapses. Results from this study also suggest the proper amount of time in vitro according to neuronal types (cortical or hippocampal) when utilized in experiments related with synaptogenesis or synaptic activities.
Animals ; Embryonic Structures ; GAP-43 Protein ; Mice ; Neurites ; Neurons ; Peripheral Nervous System ; Plastics ; Synapses ; Synaptophysin

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AMP-Activated Protein Kinase (AMPK) and Energy-Sensing in the Brain.

Santosh RAMAMURTHY ; Gabriele RONNETT

Experimental Neurobiology.2012;21(2):52-60. doi:10.5607/en.2012.21.2.52

5'-adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved cellular and organismal energy integrator that responds to numerous stimuli with the overall intention to facilitate energy conservation and enhance energy balance while also affecting cellular survival and behaviors. AMPK has been appreciated for many years to function in peripheral organs that contribute to the generation or disposition of cellular energy, while its role in the brain has been only recently elucidated. While acknowledged to respond to organismal energy balance, we now recognize that energy balance within neurons also affects the brain's response to these peripheral signals. In this review, we discuss AMPK's regulation and its ever-expanding role as a neuronal energy integrator at both the cellular and systems levels.
AMP-Activated Protein Kinases ; Brain ; Feeding Behavior ; Intention ; Neurons ; Protein Kinases ; Stroke

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The Role of Protein Phosphorylation in the Gustatory Cortex and Amygdala During Taste Learning.

Chinnakkaruppan ADAIKKAN ; Kobi ROSENBLUM

Experimental Neurobiology.2012;21(2):37-51. doi:10.5607/en.2012.21.2.37

Protein phosphorylation and dephosphorylation form a major post-translation mechanism that enables a given cell to respond to ever-changing internal and external environments. Neurons, similarly to any other cells, use protein phosphorylation/dephosphorylation to maintain an internal homeostasis, but they also use it for updating the state of synaptic and intrinsic properties, following activation by neurotransmitters and growth factors. In the present review we focus on the roles of several families of kinases, phosphatases, and other synaptic-plasticity-related proteins, which activate membrane receptors and various intracellular signals to promote transcription, translation and protein degradation, and to regulate the appropriate cellular proteomes required for taste memory acquisition, consolidation and maintenance. Attention is especially focused on the protein phosphorylation state in two forebrain areas that are necessary for taste-memory learning and retrieval: the insular cortex and the amygdala. The various temporal phases of taste learning require the activation of appropriate waves of biochemical signals. These include: extracellular signal regulated kinase I and II (ERKI/II) signal transduction pathways; Ca(2+)-dependent pathways; tyrosine kinase/phosphatase-dependent pathways; brain-derived neurotrophicfactor (BDNF)-dependent pathways; cAMP-responsive element bindingprotein (CREB); and translation-regulation factors, such as initiation and elongation factors, and the mammalian target of rapamycin (mTOR). Interestingly, coding of hedonic and aversive taste information in the forebrain requires activation of different signal transduction pathways.
Amygdala ; Clinical Coding ; Homeostasis ; Humans ; Intercellular Signaling Peptides and Proteins ; Learning ; Membranes ; Memory ; Neurons ; Neurotransmitter Agents ; Peptide Elongation Factors ; Phosphoric Monoester Hydrolases ; Phosphorylation ; Phosphotransferases ; Prosencephalon ; Proteins ; Proteolysis ; Proteome ; Signal Transduction ; Sirolimus ; Tyrosine

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Asymmetry of Dopamine D2/3 Receptor Availability in Dorsal Putamen and Body Mass Index in Non-obese Healthy Males.

Sang Soo CHO ; Eun Jin YOON ; Sang Eun KIM

Experimental Neurobiology.2015;24(1):90-94. doi:10.5607/en.2015.24.1.90

The dopaminergic system is involved in the regulation of food intake, which is crucial for the maintenance of body weight. We examined the relationship between striatal dopamine (DA) D2/3 receptor availability and body mass index (BMI) in 25 non-obese healthy male subjects using [11C]raclopride and positron emission tomography. None of [11C]raclopride binding potential (BP) values (measures of DA D2/3 receptor availability) in striatal subregions (dorsal caudate, dorsal putamen, and ventral striatum) in the left and right hemispheres was significantly correlated with BMI. However, there was a positive correlation between the right-left asymmetry index of [11C]raclopride BP in the dorsal putamen and BMI (r=0.43, p<0.05), suggesting that greater BMI is linked with higher receptor availability in the right dorsal putamen relative to the left in non-obese individuals. The present results, combined with previous findings, may also suggest neurochemical mechanisms underlying the regulation of food intake in non-obese individuals.
Body Mass Index* ; Body Weight ; Dopamine* ; Eating ; Humans ; Male ; Positron-Emission Tomography ; Putamen*

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Development of a Touch-Screen-Based Paradigm for Assessing Working Memory in the Mouse.

Chuljung KWAK ; Chae Seok LIM ; Bong Kiun KAANG

Experimental Neurobiology.2015;24(1):84-89. doi:10.5607/en.2015.24.1.84

Assessing the working memory of the rodent by using a touch-screen system has several advantages (e.g., allowing highly accurate data collection and flexibility in memory task design). However, there is currently no available testing paradigm utilizing touch-screen systems that can assess working memory in the mouse. In this study, we developed a touch-screen testing paradigm in which mice were trained to choose a location that is matched to a sample location after a time delay. Consistent with previous studies, this study showed that mice could not only learn the rule in the delayed matched to position (DMTP), but also could retain a transitory memory of the sample position during delay. This indicates that a touch-screen system can provide a DMTP testing platform to assess working memory in the mouse.
Animals ; Data Collection ; Memory ; Memory, Short-Term* ; Mice* ; Pliability ; Rodentia

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Long-term Treatment with Oriental Medicinal Herb Artemisia princeps Alters Neuroplasticity in a Rat Model of Ovarian Hormone Deficiency.

Hyun Bum KIM ; Byeong Jae KWON ; Hyun Ji CHO ; Ji Won KIM ; Jeong Woo CHON ; Moon Ho DO ; Sang Yong PARK ; Sun Yeou KIM ; Sung Ho MAENG ; Yoo Kyoung PARK ; Ji Ho PARK

Experimental Neurobiology.2015;24(1):71-83. doi:10.5607/en.2015.24.1.71

Artemisia princeps (AP) is a flowering perennial used as a traditional medicine and dietary supplement across East Asia. No study has yet assessed its effects on synaptic plasticity in hippocampus and much less in a model of ovarian hormone deficiency. We examined the influence of chronic oral AP ethanol extract treatment in ovariectomized rats on the induction of long-term depression in a representative synapse (CA3-CA1) of the hippocampus. Ovariectomized rats demonstrated lower trabecular mean bone mineral densities than sham, validating the establishment of pathology. Against this background of pathology, AP-treated ovariectomized rats exhibited attenuated long-term depression (LTD) in CA1 relative to water-treated controls as measured by increased field excitatory post-synaptic potentials (fEPSP) activation averages over the post-stimulation period. While pathological significance of long-term depression (LTD) in ovariectomized rats is conflicting, that AP treatment significantly affected its induction offers justification for further study of its influences on plasticity and its related disorders.
Animals ; Artemisia* ; Bone Density ; Depression ; Dietary Supplements ; Ethanol ; Far East ; Female ; Flowers ; Hippocampus ; Medicine, East Asian Traditional ; Medicine, Traditional ; Models, Animal* ; Neuronal Plasticity* ; Ovariectomy ; Pathology ; Plants, Medicinal* ; Plastics ; Rats ; Synapses

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COMP-Ang1 Potentiates EPC Treatment of Ischemic Brain Injury by Enhancing Angiogenesis Through Activating AKT-mTOR Pathway and Promoting Vascular Migration Through Activating Tie2-FAK Pathway.

Hyo Eun MOON ; Kyunghee BYUN ; Hyung Woo PARK ; Jin Hyun KIM ; Jin HUR ; Joong Shin PARK ; Jong Kwan JUN ; Hyo Soo KIM ; Seung Leal PAEK ; In Keyoung KIM ; Jae Ha HWANG ; Jin Wook KIM ; Dong Gyu KIM ; Young Chul SUNG ; Gou Young KOH ; Chang W SONG ; Bonghee LEE ; Sun Ha PAEK

Experimental Neurobiology.2015;24(1):55-70. doi:10.5607/en.2015.24.1.55

Successful recovery from brain ischemia is limited due to poor vascularization surrounding the ischemic zone. Cell therapy with strong angiogenic factors could be an effective strategy to rescue the ischemic brain. We investigated whether cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable and potent Ang1 variant, enhances the angiogenesis of human cord blood derived endothelial progenitor cells (hCB-EPCs) for rescuing brain from ischemic injury. COMP-Ang1 markedly improved the tube formation of capillaries by EPCs and incorporation of EPCs into tube formation with human umbilical vein endothelial cells (HUVECs) upon incubation on matrigel in vitro. COMP-Ang1 stimulated the migration of EPCs more than HUVECs in a scratch wound migration assay. The transplanted EPCs and COMP-Ang1 were incorporated into the blood vessels and decreased the infarct volume in the rat ischemic brain. Molecular studies revealed that COMP-Ang1 induced an interaction between Tie2 and FAK, but AKT was separated from the Tie2-FAK-AKT complex in the EPC plasma membrane. Tie2-FAK increased pp38, pSAPK/JNK, and pERK-mediated MAPK activation and interacted with integrins alphanubeta3, alpha4, beta1, finally leading to migration of EPCs. AKT recruited mTOR, SDF-1, and HIF-1alpha to induce angiogenesis. Taken together, it is concluded that COMP-Ang1 potentiates the angiogenesis of EPCs and enhances the vascular morphogenesis indicating that combination of EPCs with COMP-Ang1 may be a potentially effective regimen for ischemic brain injury salvage therapy.
Angiogenesis Inducing Agents ; Animals ; Blood Vessels ; Brain ; Brain Injuries* ; Brain Ischemia ; Capillaries ; Cartilage Oligomeric Matrix Protein ; Cell Membrane ; Cell- and Tissue-Based Therapy ; Fetal Blood ; Human Umbilical Vein Endothelial Cells ; Humans ; Integrins ; Ischemia ; Morphogenesis ; Rats ; Salvage Therapy ; Stem Cells ; Wounds and Injuries

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Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study.

Juhyun SONG ; Joohyun PARK ; Jae Hwan KIM ; Ja Yong CHOI ; Jae Young KIM ; Kyoung Min LEE ; Jong Eun LEE

Experimental Neurobiology.2015;24(1):41-54. doi:10.5607/en.2015.24.1.41

Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection.
Aquaporins ; Aquaporin 1 ; Ascorbic Acid ; bcl-2-Associated X Protein ; Blood-Brain Barrier ; Brain ; Brain Edema* ; Brain Injuries ; Brain Ischemia* ; Caspase 3 ; Cell Death ; Claudin-5 ; Dehydroascorbic Acid* ; Edema ; Neurons ; Nitric Oxide Synthase Type II ; Oxidative Stress ; Post-Synaptic Density ; Stroke

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