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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Research Article

Madecassic Acid Reduces Fast Transient Potassium Channels and Promotes Neurite Elongation in Hippocampal CA1 Neurons

Author(s): Sonia Siddiqui*, Faisal Khan , Khawar Saeed Jamali and Syed Ghulam Musharraf

Volume 19, Issue 1, 2020

Page: [12 - 26] Pages: 15

DOI: 10.2174/1871527318666191111105508

Price: $65

Abstract

Background and Objective: Madecassic Acid (MA) is well known to induce neurite elongation. However, its correlation with the expression of fast transient potassium (AKv) channels during neuronal development has not been well studied. Therefore, the present study was designed to investigate the effects of MA on the modulation of AKv channels during neurite outgrowth.

Methods: Neurite outgrowth was measured with morphometry software, and Kv4 currents were recorded by using the patch clamp technique.

Results: The ability of MA to promote neurite outgrowth is dose-dependent and was blocked by using the mitogen/extracellular signal-regulated kinase (MEK) inhibitor U0126. MA reduced the peak current density and surface expression of the AKv channel Kv4.2 with or without the presence of NaN3. The surface expression of Kv4.2 channels was also reduced after MA treatment of growing neurons. Ethylene glycol tetraacetic acid (EGTA) and an N-methyl-D-aspartate (NMDA) receptor blocker, MK801 along with MA prevented the effect of MA on neurite length, indicating that calcium entry through NMDA receptors is necessary for MA-induced neurite outgrowth.

Conclusion: The data demonstrated that MA increased neurite outgrowth by internalizing AKv channels in neurons. Any alterations in the precise density of ion channels can lead to deleterious consequences on health because it changes the electrical and mechanical function of a neuron or a cell. Modulating ion channel’s density is exciting research in order to develop novel drugs for the therapeutic treatment of various diseases of CNS.

Keywords: Neurite outgrowth, Centella asiatica, madecassic acid, hippocampal neuron, NMDA, patch clamp.

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[1]
Soumyanath, A.; Zhong, Y.P.; Gold, S.A. Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in-vitro. J. Pharm. Pharmacol., 2005, 57(9), 1221-9.
[http://dx.doi.org/10.1211/jpp.57.9.0018] [PMID: 16105244]
[2]
Lee, M.K.; Kim, S.R.; Sung, S.H. Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. Res. Commun. Mol. Pathol. Pharmacol., 2000, 108(1-2), 75-86.
[PMID: 11758977]
[3]
Rao, S.B.; Chetana, M.; Uma Devi, P. Centella asiatica treatment during postnatal period enhances learning and memory in mice. Physiol. Behav., 2005, 86(4), 449-457.
[http://dx.doi.org/10.1016/j.physbeh.2005.07.019] [PMID: 16214185]
[4]
Soumyanath, A.; Gold, B.; Gold, S.; Zhong, Y.P.; Bourdette, D. Methods and compositions for nerve regeneration. US Patent 20070196522 A1 2007.
[5]
Mohandas Rao, K.G.; Muddanna Rao, S.; Gurumadhva Rao, S. Centella asiatica (L.) leaf extract treatment during the growth spurt period enhances hippocampal CA3 neuronal dendritic arborization in rats. Evid. Based Complement. Alternat. Med., 2006, 3(3), 349-357.
[http://dx.doi.org/10.1093/ecam/nel024] [PMID: 16951719]
[6]
Lei, Z.; Deng, P.; Li, Y.; Xu, Z.C. Downregulation of Kv4.2 channels mediated by NR2B-containing NMDA receptors in cultured hippocampal neurons. Neuroscience, 2010, 165(2), 350-362.
[http://dx.doi.org/10.1016/j.neuroscience.2009.10.041] [PMID: 19857555]
[7]
Fontán-Lozano, Á.; Suárez-Pereira, I.; González-Forero, D.; Carrión, A.M. The A-current modulates learning via NMDA receptors containing the NR2B subunit. PLoS One, 2011, 6(9)e24915
[http://dx.doi.org/10.1371/journal.pone.0024915] [PMID: 21966384]
[8]
Alfaro-Ruíz, R.; Aguado, C.; Martín-Belmonte, A.; Moreno-Martínez, A.E.; Luján, R. Expression, cellular and subcellular localisation of Kv4.2 and Kv4.3 channels in the rodent hippocampus. Int. J. Mol. Sci., 2019, 20(2), 246.
[http://dx.doi.org/10.3390/ijms20020246] [PMID: 30634540]
[9]
Rhodes, K.J.; Carroll, K.I.; Sung, M.A. KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain. J. Neurosci., 2004, 24(36), 7903-15.
[http://dx.doi.org/10.1523/JNEUROSCI.0776-04.2004] [PMID: 15356203]
[10]
Kim, J.; Wei, D.S.; Hoffman, D.A. Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones. J. Physiol., 2005, 569(Pt 1), 41-57.
[http://dx.doi.org/10.1113/jphysiol.2005.095042] [PMID: 16141270]
[11]
Fontán-Lozano, A.; Suárez-Pereira, I.; Delgado-García, J.M.; Carrión, A.M. The M-current inhibitor XE991 decreases the stimulation threshold for long-term synaptic plasticity in healthy mice and in models of cognitive disease. Hippocampus, 2011, 21(1), 22-32.
[http://dx.doi.org/10.1002/hipo.20717] [PMID: 19921704]
[12]
Li, L.; Li, D.P.; Chen, S.R.; Chen, J.; Hu, H.; Pan, H.L. Potentiation of high voltage-activated calcium channels by 4-aminopyridine depends on subunit composition. Mol. Pharmacol., 2014, 86(6), 760-772.
[http://dx.doi.org/10.1124/mol.114.095505]
[13]
Yunoki, T.; Takimoto, K.; Kita, K. Differential contribution of Kv4-containing channels to A-type, voltage-gated potassium currents in somatic and visceral dorsal root ganglion neurons. J. Neurophysiol., 2014, 112(10), 2492-2504.
[http://dx.doi.org/10.1152/jn.00054]
[14]
Biró, Á.A.; Brémaud, A.; Falck, J.; Ruiz, A.J. A-type K+ channels impede supralinear summation of clustered glutamatergic inputs in layer 3 neocortical pyramidal neurons. Neuropharmacology, 2018, 140, 86-99.
[http://dx.doi.org/10.1016/j.neuropharm.2018.07.005] [PMID: 30009837]
[15]
Shibata, R.; Nakahira, K.; Shibasaki, K.; Wakazono, Y.; Imoto, K.; Ikenaka, K. A-type K+ current mediated by the Kv4 channel regulates the generation of action potential in developing cerebellar granule cells. J. Neurosci., 2000, 20(11), 4145-4155.
[http://dx.doi.org/10.1523/JNEUROSCI.20-11-04145.2000] [PMID: 10818150]
[16]
Wilson, M.T.; Kisaalita, W.S.; Keith, C.H. Glutamate-induced changes in the pattern of hippocampal dendrite outgrowth: a role for calcium-dependent pathways and the microtubule cytoskeleton. J. Neurobiol., 2000, 43(2), 159-172.
[http://dx.doi.org/10.1002/(sici)1097-4695(200005)43:2<159:aid-neu6>3.0.co;2-n] [PMID: 10770845]
[17]
Maletic-Savatic, M.; Lenn, N.J.; Trimmer, J.S. Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro. J. Neurosci., 1995, 15(5 Pt 2), 3840-3851.
[http://dx.doi.org/10.1523/JNEUROSCI.15-05-03840.1995] [PMID: 7751950]
[18]
Huang, Y.; Ma, S.; Wang, Y. The role of traditional Chinese herbal medicines and bioactive ingredients on ion channels: a brief review and prospect. CNS Neurol. Disord. Drug Targets, 2019, 18(4), 257-265.
[http://dx.doi.org/10.2174/1871527317666181026165400] [PMID: 30370864]
[19]
Zhu, Y.; Zhang, S.; Feng, Y.; Xiao, Q.; Cheng, J.; Tao, J. The yin and yang of BK channels in epilepsy. CNS Neurol. Disord. Drug Targets, 2018, 17(4), 272-9.
[http://dx.doi.org/10.2174/1871527317666180213142403] [PMID: 29437015]
[20]
Zang, K.; Zhang, Y.; Hu, J.; Wang, Y. The large conductance calcium- and voltage-activated potassium channel (BK) and epilepsy. CNS Neurol. Disord. Drug Targets, 2018, 17(4), 248-254.
[http://dx.doi.org/10.2174/1871527317666180404104055] [PMID: 29623857]
[21]
Yang, J.; Yan, X. Oxidation of potassium channels in ceurodegenerative diseases: a mini-review. CNS Neurol. Disord. Drug Targets, 2018, 17(4), 267-271.
[http://dx.doi.org/10.2174/1871527317666180202110056] [PMID: 29422009]
[22]
Khalid, R.; Noureen, N.; Kamal, M.A.; Batool, S. Computational protein-protein docking revealing the therapeutic potential of Kunitz-type venom against hKv1.2 binding sites. CNS Neurol. Disord. Drug Targets, 2019, 18(5), 382-404.
[http://dx.doi.org/10.2174/1871527318666190319140204] [PMID: 30892167]
[23]
Csabai, D.; Wiborg, O.; Czéh, B. Reduced synapse and axon numbers in the prefrontal cortex of rats subjected to a chronic stress model for depression. Front. Cell. Neurosci., 2018, 12, 24.
[http://dx.doi.org/10.3389/fncel.2018.00024] [PMID: 29440995]
[24]
Salvadores, N.; Sanhueza, M.; Manque, P.; Court, F.A. Axonal degeneration during aging and its functional role in neurodegenerative disorders. Front. Neurosci., 2017, 11, 451.
[http://dx.doi.org/10.3389/fnins.2017.00451]
[25]
Siddiqui, S.; Kamal, A.; Khan, F.; Jamali, K.S.; Saify, Z.S. Gallic and vanillic acid suppress inflammation and promote myelination in an in vitro mouse model of neurodegeneration. Mol. Biol. Rep., 2019, 46(1), 997-1011.
[http://dx.doi.org/10.1007/s11033-018-4557-1] [PMID: 30569390]
[26]
Siddiqui, S.; Saify, Z.S.; Jamali, K.S. Neuroprotective capabilities of Vitex negundo in primary hippocampal neurons. Pak. J. Pharm. Sci., 2018, 31(1(Suppl.)), 341-44.
[27]
Song, W.J.; Tkatch, T.; Baranauskas, G.; Ichinohe, N.; Kitai, S.T.; Surmeier, D.J. Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the A type and attributable to coexpression of Kv4.2 and Kv4.1 subunits. J. Neurosci., 1998, 18(9), 3124-37.
[http://dx.doi.org/10.1523/JNEUROSCI.18-09-03124.1998] [PMID: 9547221]
[28]
Amberg, G.C.; Koh, S.D.; Hatton, W.J. Contribution of Kv4 channels toward the A-type potassium current in murine colonic myocytes. J. Physiol., 2002, 544(2), 403-15.
[http://dx.doi.org/10.1113/jphysiol.2002.025163] [PMID: 12381814]
[29]
Shibasaki, K.; Nakahira, K.; Trimmer, J.S. Mossy fibre contact triggers the targeting of Kv4.2 potassium channels to dendrites and synapses in developing cerebellar granule neurons. J. Neurochem., 2004, 89(4), 897-907.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02368.x] [PMID: 15140189]
[30]
Siddiqui, S.; Horvat-Broecker, A.; Faissner, A. Comparative screening of glial cell types reveals extracellular matrix that inhibits retinal axon growth in a chondroitinase ABC-resistant fashion. Glia, 2009, 57(13), 1420-38.
[http://dx.doi.org/10.1002/glia.20860] [PMID: 19243018]
[31]
Schrader, L.A.; Birnbaum, S.G.; Nadin, B.M. ERK/MAPK regulates the Kv4.2 potassium channel by direct phosphorylation of the pore-forming subunit. Am. J. Physiol. Cell Physiol., 2006, 290(3), C852-61.
[http://dx.doi.org/10.1152/ajpcell.00358.2005] [PMID: 16251476]
[32]
Pollock, N.S.; Atkinson-Leadbeater, K.; Johnston, J.; Larouche, M.; Wildering, W.C.; McFarlane, S. Voltage-gated potassium channels regulate the response of retinal growth cones to axon extension and guidance cues. Eur. J. Neurosci., 2005, 22(3), 569-578.
[http://dx.doi.org/10.1111/j.1460-9568.2005.04242.x] [PMID: 16101738]
[33]
Walker, M.P.; Cowlen, M.; Christensen, D.; Miyamoto, M.; Barley, P.; Crowder, T. Nonclinical safety assessment of SPX-101, a novel peptide promoter of epithelial sodium channel internalization for the treatment of cystic fibrosis. Inhal. Toxicol., 2017, 29(8), 356-365.
[34]
Cohan, C.H.; Stradecki-Cohan, H.M.; Morris-Blanco, K.C. Protein kinase C epsilon delays latency until anoxic depolarization through arc expression and GluR2 internalization. J. Cereb. Blood Flow Metab., 2017, 37(12), 3774-3788.
[http://dx.doi.org/10.1177/0271678X17712178] [PMID: 28585865]
[35]
Tang, B.L.K. K+-Cl- co-transporter 2 (KCC2) - a membrane trafficking perspective. Mol. Membr. Biol., 2016, 33(6-8), 100-10.
[http://dx.doi.org/10.1080/09687688.2017.1393566]
[36]
Li, A.; Yau, S.Y.; Machado, S.; Wang, P.; Yuan, T.F.; So, K.F. Enhancement of hippocampal plasticity by physical exercise as a polypill for stress and depression. CNS Neurol. Disord. Drug Targets, 2019, 18(4), 294-306.
[http://dx.doi.org/10.2174/1871527318666190308102804] [PMID: 30848219]
[37]
Farhat, S.M.; Ahmed, T. Aluminum suppresses effect of nicotine on gamma oscillations (20-40 Hz) in mouse hippocampal slices. CNS Neurol. Disord. Drug Targets, 2018, 17(6), 404-11.
[http://dx.doi.org/10.2174/1871527317666180619155644] [PMID: 29921211]
[38]
Shiha, A.A.; de la Rosa, R.F.; Delgado, M.; Pozo, M.A.; García-García, L. Subacute fluoxetine reduces signs of hippocampal damage induced by a single convulsant dose of 4-aminopyridine in rats. CNS Neurol. Disord. Drug Targets, 2017, 16(6), 694-704.
[http://dx.doi.org/10.2174/1871527315666160720121723] [PMID: 27989232]
[39]
Wei, X.; Yang, D.; Shi, T. Metabotropic glutamate receptor 7 (mGluR7) as a target for modulating pain-evoked activities of neurons in the hippocampal CA3 region of rats. CNS Neurol. Disord. Drug Targets, 2017, 16(5), 610-6.
[http://dx.doi.org/10.2174/1871527315666160801142356] [PMID: 27488423]
[40]
Lugo, J.N.; Barnwell, L.F.; Ren, Y. Altered phosphorylation and localization of the A-type channel, Kv4.2 in status epilepticus. J. Neurochem., 2008, 106(4), 1929-40.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05508.x] [PMID: 18513371]
[41]
Hu, H.J.; Gereau, R.W., 4th ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. II. Modulation of neuronal excitability. J. Neurophysiol., 2003, 90(3), 1680-1688.
[http://dx.doi.org/10.1152/jn.00341.2003] [PMID: 12750418]
[42]
Luther, J.A.; Birren, S.J. Nerve growth factor decreases potassium currents and alters repetitive firing in rat sympathetic neurons. J. Neurophysiol., 2006, 96(2), 946-958.
[http://dx.doi.org/10.1152/jn.01078.2005] [PMID: 16707716]
[43]
Leng, J.; Jiang, L.; Chen, H.; Zhang, X. Brain-derived neurotrophic factor and electrophysiological properties of voltage-gated ion channels during neuronal stem cell development. Brain Res., 2009, 1272, 14-24.
[http://dx.doi.org/10.1016/j.brainres.2009.03.048] [PMID: 19344696]
[44]
Kim, J.; Jung, S.C.; Clemens, A.M.; Petralia, R.S.; Hoffman, D.A. Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons. Neuron, 2007, 54(6), 933-947.
[http://dx.doi.org/10.1016/j.neuron.2007.05.026] [PMID: 17582333]
[45]
Jugloff, D.G.; Khanna, R.; Schlichter, L.C.; Jones, O.T. Internalization of the Kv1.4 potassium channel is suppressed by clustering interactions with PSD-95. J. Biol. Chem., 2000, 275(2), 1357-1364.
[http://dx.doi.org/10.1074/jbc.275.2.1357] [PMID: 10625685]
[46]
Oertner, T.G.; Matus, A. Calcium regulation of actin dynamics in dendritic spines. Cell Calcium, 2005, 37(5), 477-482.
[http://dx.doi.org/10.1016/j.ceca.2005.01.016] [PMID: 15820396]
[47]
Kim, J.; Kwon, J.T.; Kim, H.S.; Josselyn, S.A.; Han, J.H. Memory recall and modifications by activating neurons with elevated CREB. Nat. Neurosci., 2014, 17(1), 65-72.
[http://dx.doi.org/10.1038/nn.3592] [PMID: 24212670]
[48]
Jung, S-C.; Hoffman, D.A. Biphasic somatic A-type K channel downregulation mediates intrinsic plasticity in hippocampal CA1 pyramidal neurons. PLoS One, 2009, 4(8)e6549
[http://dx.doi.org/10.1371/journal.pone.0006549] [PMID: 19662093]
[49]
Kerti, K.; Lorincz, A.; Nusser, Z. Unique somato-dendritic distribution pattern of Kv4.2 channels on hippocampal CA1 pyramidal cells. Eur. J. Neurosci., 2012, 35(1), 66-75.
[http://dx.doi.org/10.1111/j.1460-9568.2011.07907.x] [PMID: 22098631]
[50]
Cooper, E.C.; Milroy, A.; Jan, Y.N.; Jan, L.Y.; Lowenstein, D.H. Presynaptic localization of Kv1.4-containing A-type potassium channels near excitatory synapses in the hippocampus. J. Neurosci., 1998, 18(3), 965-974.
[http://dx.doi.org/10.1523/JNEUROSCI.18-03-00965.1998] [PMID: 9437018]
[51]
Chen, X.; Yuan, L.L.; Zhao, C. Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons. J. Neurosci., 2006, 26(47), 12143-12151.
[http://dx.doi.org/10.1523/JNEUROSCI.2667-06.2006] [PMID: 17122039]
[52]
Varga, A.W.; Anderson, A.E.; Adams, J.P.; Vogel, H.; Sweatt, J.D. Input-specific immunolocalization of differentially phosphorylated Kv4.2 in the mouse brain. Learn. Mem., 2000, 7(5), 321-332.
[http://dx.doi.org/10.1101/lm.35300] [PMID: 11040264]

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