Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Upregulation of Connexins in the Rat Hippocampal and Cortical Neurons Following Blockade of NMDA Receptors During Postnatal Development

Author(s): Masoumeh Kourosh-Arami*, Mansoureh Soleimani, Mohammad Taghi Joghataei, Masoumeh Mosleh, Parisa Hayat and Alireza Komaki

Volume 30, Issue 1, 2023

Published on: 25 November, 2022

Page: [65 - 71] Pages: 7

DOI: 10.2174/0929866530666221024153723

Price: $65

Abstract

Background: Interneural gap junctional coupling represents neural development that decreases during the postnatal period. The decrease of gap junction function coincides with the main period of chemical synapse creation and increment of synaptic activity during postnatal weeks 1 to 3.

Methods: Here, we have assessed the role of chemical synapses on connexin (Cx) expression in neurons and glial cells of hippocampal and cortical neurons. We characterized the impact of NMDA receptors blockade on the expression of Cx36 and Cx43 proteins by western blot analysis in postnatal day (PND)14 and PND28. MK801 was injected subcutaneously from the first day of birth until 14 or 28 days, depending on the experimental groups. Saline was injected in the same volumes in the control group.

Results: Early postnatal blockade of the NMDA subtype of glutamate receptors by the non-competitive antagonist dizocilpine maleate (MK801) arrested the developmental reduction in gap junctions during the initial postnatal weeks. Expression of Cx43 declined in PND28 compared to PND14 in visual cortex (VC) neurons. Also, we found that the expression of Cx36 and Cx43 augmented in the rats' VC in PND28 following the blockade of NMDA receptors. Expression of Cx36 declined in PND28 compared to PND14 in hippocampal neurons. Also, we found that the expression of Cx36 augmented in the rats' hippocampal neurons in PND14 and PND28 following a blockade of NMDA receptors.

Conclusion: These results suggest that the postnatal enhancement in glutamatergic synaptic activity is associated with the loss of gap junctional connections and downregulation of Cx36 and Cx43 between developing neurons and glial cells.

« Previous Next »
Graphical Abstract

[1]
Chang, Q.; Gonzalez, M.; Pinter, M.J.; Balice, G.R.J. Gap junctional coupling and patterns of connexin expression among neonatal rat lumbar spinal motor neurons. J. Neurosci., 1999, 19(24), 10813-10828.
[http://dx.doi.org/10.1523/JNEUROSCI.19-24-10813.1999] [PMID: 10594064]
[2]
Mentis, G.Z.; Díaz, E.; Moran, L.B.; Navarrete, R. Increased incidence of gap junctional coupling between spinal motoneurones following transient blockade of NMDA receptors in neonatal rats. J. Physiol., 2002, 544(3), 757-764.
[http://dx.doi.org/10.1113/jphysiol.2002.028159] [PMID: 12411521]
[3]
Niculescu, D.; Lohmann, C. Gap junctions in developing thalamic and neocortical neuronal networks. Cereb. Cortex, 2014, 24(12), 3097-3106.
[http://dx.doi.org/10.1093/cercor/bht175] [PMID: 23843439]
[4]
Dermietzel, R.; Spray, D.C. Gap junctions in the brain: Where, what type, how many and why? Trends Neurosci., 1993, 16(5), 186-192.
[http://dx.doi.org/10.1016/0166-2236(93)90151-B] [PMID: 7685944]
[5]
Kumar, N.M.; Gilula, N.B. The gap junction communication channel. Cell, 1996, 84(3), 381-388.
[http://dx.doi.org/10.1016/S0092-8674(00)81282-9] [PMID: 8608591]
[6]
Nadarajah, B.; Jones, A.M.; Evans, W.H.; Parnavelas, J.G. Differential expression of connexins during neocortical development and neuronal circuit formation. J. Neurosci., 1997, 17(9), 3096-3111.
[http://dx.doi.org/10.1523/JNEUROSCI.17-09-03096.1997] [PMID: 9096144]
[7]
Rash, J.E.; Olson, C.O.; Davidson, K.G.V.; Yasumura, T.; Kamasawa, N.; Nagy, J.I. Identification of connexin 36 in gap junctions between neurons in rodent locus coeruleus. Neuroscience, 2007, 147(4), 938-956.
[http://dx.doi.org/10.1016/j.neuroscience.2007.04.061] [PMID: 17601673]
[8]
Lee, I.H.; Lindqvist, E.; Kiehn, O.; Widenfalk, J.; Olson, L. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury. J. Comp. Neurol., 2005, 489(1), 1-10.
[http://dx.doi.org/10.1002/cne.20567] [PMID: 15977163]
[9]
Belousov, A.B. The regulation and role of neuronal gap junctions during development. Commun. Integr. Biol., 2011, 4(5), 579-581.
[http://dx.doi.org/10.4161/cib.16380] [PMID: 22046468]
[10]
Park, W.M.; Wang, Y.; Park, S.; Denisova, J.V.; Fontes, J.D.; Belousov, A.B. Interplay of chemical neurotransmitters regulates developmental increase in electrical synapses. J. Neurosci., 2011, 31(16), 5909-5920.
[http://dx.doi.org/10.1523/JNEUROSCI.6787-10.2011] [PMID: 21508216]
[11]
Arumugam, H.; Liu, X.; Colombo, P.J.; Corriveau, R.A.; Belousov, A.B. NMDA receptors regulate developmental gap junction uncoupling via CREB signaling. Nat. Neurosci., 2005, 8(12), 1720-1726.
[http://dx.doi.org/10.1038/nn1588] [PMID: 16299502]
[12]
Kandler, K.; Thiels, E. Flipping the switch from electrical to chemical communication. Nat. Neurosci., 2005, 8(12), 1633-1634.
[http://dx.doi.org/10.1038/nn1205-1633] [PMID: 16306887]
[13]
Leung, D.S.Y.; Unsicker, K.; Reuss, B. Expression and developmental regulation of gap junction connexins cx26, cx32, cx43 and cx45 in the rat midbrain‐floor. Int. J. Dev. Neurosci., 2002, 20(1), 63-75.
[http://dx.doi.org/10.1016/S0736-5748(01)00056-9] [PMID: 12008076]
[14]
Personius, K.E.; Karnes, J.L.; Parker, S.D. NMDA receptor blockade maintains correlated motor neuron firing and delays synapse competition at developing neuromuscular junctions. J. Neurosci., 2008, 28(36), 8983-8992.
[http://dx.doi.org/10.1523/JNEUROSCI.5226-07.2008] [PMID: 18768692]
[15]
Alvarez, M.V.; García, H.F.; Williams, J.T.; Van Bockstaele, E.J. Functional coupling between neurons and glia. J. Neurosci., 2000, 20(11), 4091-4098.
[http://dx.doi.org/10.1523/JNEUROSCI.20-11-04091.2000] [PMID: 10818144]
[16]
Rash, J.E.; Staines, W.A.; Yasumura, T.; Patel, D.; Furman, C.S.; Stelmack, G.L.; Nagy, J.I. Immunogold evidence that neuronal gap junctions in adult rat brain and spinal cord contain connexin-36 but not connexin-32 or connexin-43. Proc. Natl. Acad. Sci., 2000, 97(13), 7573-7578.
[http://dx.doi.org/10.1073/pnas.97.13.7573] [PMID: 10861019]
[17]
Belousov, A.B. Novel model for the mechanisms of glutamate-dependent excitotoxicity: Role of neuronal gap junctions. Brain Res., 2012, 1487, 123-130.
[http://dx.doi.org/10.1016/j.brainres.2012.05.063] [PMID: 22771704]
[18]
Pereda, A.E.; Curti, S.; Hoge, G.; Cachope, R.; Flores, C.E.; Rash, J.E. Gap junction-mediated electrical transmission: Regulatory mechanisms and plasticity. Biochim. Biophys. Acta Biomembr., 2013, 1828(1), 134-146.
[http://dx.doi.org/10.1016/j.bbamem.2012.05.026] [PMID: 22659675]
[19]
Belousov, A.B.; Fontes, J.D. Neuronal gap junctions: Making and breaking connections during development and injury. Trends Neurosci., 2013, 36(4), 227-236.
[http://dx.doi.org/10.1016/j.tins.2012.11.001] [PMID: 23237660]
[20]
Bennett, M.V.L.; Zukin, R.S. Electrical coupling and neuronal synchronization in the mammalian brain. Neuron, 2004, 41(4), 495-511.
[http://dx.doi.org/10.1016/S0896-6273(04)00043-1] [PMID: 14980200]
[21]
Gulisano, M.; Parenti, R.; Spinella, F.; Cicirata, F. C×36 is dynamically expressed during early development of mouse brain and nervous system. Neuroreport, 2000, 11(17), 3823-3828.
[http://dx.doi.org/10.1097/00001756-200011270-00045] [PMID: 11117498]
[22]
Prime, G.; Horn, G.; Sutor, B. Time-related changes in connexin mRNA abundance in the rat neocortex during postnatal development. Brain Res. Dev. Brain Res., 2000, 119(1), 111-125.
[http://dx.doi.org/10.1016/S0165-3806(99)00132-7] [PMID: 10648878]
[23]
Moore, K.B.; O’Brien, J. Connexins in neurons and glia: Targets for intervention in disease and injury. Neural Regen. Res., 2015, 10(7), 1013-1017.
[http://dx.doi.org/10.4103/1673-5374.160092] [PMID: 26330808]
[24]
Hartfield, E.M.; Rinaldi, F.; Glover, C.P.; Wong, L.F.; Caldwell, M.A.; Uney, J.B. Connexin 36 expression regulates neuronal differentiation from neural progenitor cells. PLoS One, 2011, 6(3), e14746.
[http://dx.doi.org/10.1371/journal.pone.0014746] [PMID: 21408068]
[25]
De Rivero, V.J.C.; Corriveau, R.A.; Belousov, A.B. Gap junctions are required for NMDA receptor dependent cell death in developing neurons. J. Neurophysiol., 2007, 98(5), 2878-2886.
[http://dx.doi.org/10.1152/jn.00362.2007] [PMID: 17855590]
[26]
Song, J.H.; Wang, Y.; Fontes, J.D.; Belousov, A.B. Regulation of connexin 36 expression during development. Neurosci. Lett., 2012, 513(1), 17-19.
[http://dx.doi.org/10.1016/j.neulet.2012.01.075] [PMID: 22342304]
[27]
Armstrong, D.L.; Turin, L.; Warner, A.E. Muscle activity and the loss of electrical coupling between striated muscle cells in Xenopus embryos. J. Neurosci., 1983, 3(7), 1414-1421.
[http://dx.doi.org/10.1523/JNEUROSCI.03-07-01414.1983] [PMID: 6306176]
[28]
Kandler, K.; Katz, L.C. Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication. J. Neurosci., 1998, 18(4), 1419-1427.
[http://dx.doi.org/10.1523/JNEUROSCI.18-04-01419.1998] [PMID: 9454851]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy