Postnatal Neuronal Nogo-A Knockdown Decreased the Message of Glutamatergic Synaptic Proteins.
Animals
Nogo Proteins
/ metabolism
Rats
Receptors, N-Methyl-D-Aspartate
/ metabolism
Myelin Proteins
/ genetics
Disks Large Homolog 4 Protein
/ metabolism
Rats, Sprague-Dawley
Synapses
/ metabolism
Vesicular Glutamate Transport Protein 1
/ metabolism
Gene Knockdown Techniques
Neuronal Plasticity
/ physiology
Pyramidal Cells
/ metabolism
Membrane Proteins
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Neurons
/ metabolism
Animals, Newborn
Sensorimotor Cortex
/ metabolism
RNA, Messenger
/ metabolism
Guanylate Kinases
/ genetics
Vesicular Glutamate Transport Protein 2
Journal
Journal of physiological investigation
ISSN: 2950-6344
Titre abrégé: J Physiol Investig
Pays: India
ID NLM: 9918803386606676
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
received:
26
06
2024
accepted:
09
09
2024
medline:
28
10
2024
pubmed:
28
10
2024
entrez:
28
10
2024
Statut:
ppublish
Résumé
It is well known that oligodendrocyte-associated Nogo-A protein is an important regulator of axonal outgrowth and an important inhibitor of functional recovery and anatomical plasticity after central nervous system (CNS) injury. Abundant studies of oligodendrocyte-associated Nogo-A function in the uninjured rodent have suggested a role in neuronal development and synaptic function. On the other hand, the roles of neuron-associated (i.e., neuronal) Nogo-A have not been fully investigated. We have previously shown that neuronal Nogo-A influence dendritic spine density and morphology in pyramidal neurons of the intact neocortex. To further examine the role of neuronal Nogo-A in this synaptic population, we designed an RNAi directed against Nogo-A, delivered to the developing rat sensorimotor cortex using a neurotropic viral vector adeno-associated virus (AAV) 2/8. We examined the transduced neocortex for molecules important for synaptic plasticity, including N-Methyl-D-Aspartate (NMDA) receptor subunits GRIN2A; glutamate receptor subunit epsilon-1 (NR2A), and GRIN2B; glutamate receptor subunit epsilon-2 (NR2B), as well as postsynaptic density-95 (PSD-95). Furthermore, we also determined the density of excitatory synapses by examining the presynaptic protein vesicular glutamate transporter 1 (vGLut1) as a marker for potential excitatory synapses. Our results showed that neuronal Nogo-A knockdown in postnatal pyramidal neurons of the sensorimotor cortex led to a significant decrease in NMDA receptor subunits NR2A and NR2B messenger RNA when examined as adults. However, there was no difference in PSD-95 expression in comparison to controls. In addition, the decrease in the number of vGlut1(+) puncta on branches of apical dendrites of pyramidal neurons indicated the loss of synapses that have a strong influence on direct current entering the dendrite. Taken together, these results indicate that neuronal Nogo-A may regulate synaptic plasticity by modulating the components of excitatory synapses. This finding represents a novel role in excitatory synaptic formation for neuronal Nogo-A in developing neurons of the uninjured CNS.
Identifiants
pubmed: 39465566
doi: 10.4103/ejpi.EJPI-D-24-00063
pii: 02275668-202467050-00003
doi:
Substances chimiques
Nogo Proteins
0
Receptors, N-Methyl-D-Aspartate
0
Rtn4 protein, rat
0
Myelin Proteins
0
Disks Large Homolog 4 Protein
0
Dlg4 protein, rat
0
Vesicular Glutamate Transport Protein 1
0
NR2B NMDA receptor
0
N-methyl D-aspartate receptor subtype 2A
VH92ICR8HX
Membrane Proteins
0
Slc17a7 protein, rat
0
Intracellular Signaling Peptides and Proteins
0
Slc17a6 protein, rat
0
RNA, Messenger
0
Guanylate Kinases
EC 2.7.4.8
Vesicular Glutamate Transport Protein 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
249-257Informations de copyright
Copyright © 2024 Copyright: © 2024 Journal of Physiological Investigation.
Références
Schwab ME, Strittmatter SM Nogo limits neural plasticity and recovery from injury. Curr Opin Neurobiol 2014; 27: 53–60.
Harel NY, Strittmatter SM Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury?. Nat Rev Neurosci 2006; 7: 603–16.
Chen K, Marsh BC, Cowan M, Al'Joboori YD, Gigout S, Smith CC, et al. Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats. Exp Neurol 2017; 292: 135–44.
Deng Q, Cai W, Li S, Zhang Y, Su B Small nogo-66-binding peptide promotes neurite outgrowth through RhoA inhibition after spinal cord injury. Brain Res Bull 2013; 99: 140–4.
Freund P, Wannier T, Schmidlin E, Bloch J, Mir A, Schwab ME, et al. Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey. J Comp Neurol 2007; 502: 644–59.
Mohammed R, Opara K, Lall R, Ojha U, Xiang J Evaluating the effectiveness of anti-nogo treatment in spinal cord injuries. Neural Dev 2020; 15: 1.
Schnell L, Hunanyan AS, Bowers WJ, Horner PJ, Federoff HJ, Gullo M, et al. Combined delivery of Nogo-A antibody, neurotrophin-3 and the NMDA-NR2d subunit establishes a functional 'detour'in the hemisected spinal cord. Eur J Neurosci 2011; 34: 1256–67.
Walmsley AR, Mir AK Targeting the Nogo-a signalling pathway to promote recovery following acute CNS injury. Curr Pharm Des 2007; 13: 2470–84.
Markus TM, Tsai SY, Bollnow MR, Farrer RG, O'Brien TE, Kindler-Baumann DR, et al. Recovery and brain reorganization after stroke in adult and aged rats. Ann Neurol 2005; 58: 950–3.
Cheatwood JL, Emerick AJ, Kartje GL Neuronal plasticity and functional recovery after ischemic stroke. Top Stroke Rehabil 2008; 15: 42–50.
Podraza KM, Mehta Y, Husak VA, Lippmann E, O'Brien TE, Kartje GL, et al. Improved functional outcome after chronic stroke with delayed anti-Nogo-A therapy: A clinically relevant intention-to-treat analysis. J Cereb Blood Flow Metab 2018; 38: 1327–38.
Papadopoulos CM, Tsai SY, Alsbiei T, O'Brien TE, Schwab ME, Kartje GL Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat. Ann Neurol 2002; 51: 433–41.
Seymour AB, Andrews EM, Tsai SY, Markus TM, Bollnow MR, Brenneman MM, et al. Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats. J Cereb Blood Flow Metab 2005; 25: 1366–75.
Lenzlinger PM, Shimizu S, Marklund N, Thompson HJ, Schwab ME, Saatman KE, et al. Delayed inhibition of Nogo-A does not alter injury-induced axonal sprouting but enhances recovery of cognitive function following experimental traumatic brain injury in rats. Neuroscience 2005; 134: 1047–56.
Powers BE, Ton ST, Farrer RG, Chaudhary S, Nockels RP, Kartje GL, et al. Anti-Nogo-A antibody therapy improves functional outcome following traumatic brain injury. Neurorehabil Neural Repair 2023; 37: 682–93.
Kucher K, Johns D, Maier D, Abel R, Badke A, Baron H, et al. First-in-man intrathecal application of neurite growth-promoting anti-Nogo-A antibodies in acute spinal cord injury. Neurorehabil Neural Repair 2018; 32: 578–89.
Zörner B, Schwab ME Anti-Nogo on the go: From animal models to a clinical trial. Ann N Y Acad Sci 2010 1198 Suppl 1 E22–34.
Huber AB, Weinmann O, Brösamle C, Oertle T, Schwab ME Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions. J Neurosci 2002; 22: 3553–67.
Mingorance-Le Meur A, Zheng B, Soriano E, del Río JA Involvement of the myelin-associated inhibitor Nogo-A in early cortical development and neuronal maturation. Cereb Corte× 2007; 17: 2375–86.
Cheatwood JL, Emerick AJ, Schwab ME, Kartje GL Nogo-A expression after focal ischemic stroke in the adult rat. Stroke 2008; 39: 2091–8.
Hunt D, Coffin RS, Prinjha RK, Campbell G, Anderson PN Nogo-A expression in the intact and injured nervous system. Mol Cell Neurosci 2003; 24: 1083–102.
Shepherd DJ, Tsai SY, O'Brien TE, Farrer RG, Kartje GL Anti-Nogo-A immunotherapy does not alter hippocampal neurogenesis after stroke in adult rats. Front Neurosci 2016; 10: 467.
Shepherd DJ, Tsai SY, Cappucci SP, Wu JY, Farrer RG, Kartje GL The subventricular zone response to stroke is not a therapeutic target of anti-Nogo-A immunotherapy. J Neuropathol Exp Neurol 2017; 76: 683–96.
Li X, Su H, Fu QL, Guo J, Lee DH, So KF, et al. Soluble NgR fusion protein modulates the proliferation of neural progenitor cells via the Notch pathway. Neurochem Res 2011; 36: 2363–72.
Zhao X, Wu J, Kuang F, Wang J, Ju G Silencing of Nogo-A in rat oligodendrocyte cultures enhances process branching. Neurosci Lett 2011; 499: 32–6.
Cafferty WB, Duffy P, Huebner E, Strittmatter SM MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma. J Neurosci 2010; 30: 6825–37.
Pernet V, Joly S, Christ F, Dimou L, Schwab ME Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation. J Neurosci 2008; 28: 7435–44.
Wang X, Chun SJ, Treloar H, Vartanian T, Greer CA, Strittmatter SM Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact. J Neurosci 2002; 22: 5505–15.
Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403: 434–9.
Pradhan AD, Case AM, Farrer RG, Tsai SY, Cheatwood JL, Martin JL, et al. Dendritic spine alterations in neocortical pyramidal neurons following postnatal neuronal Nogo-A knockdown. Dev Neurosci 2010; 32: 313–20.
Alvarez VA, Ridenour DA, Sabatini BL Distinct structural and ionotropic roles of NMDA receptors in controlling spine and synapse stability. J Neurosci 2007; 27: 7365–76.
Chen BS, Thomas EV, Sanz-Clemente A, Roche KW NMDA receptor-dependent regulation of dendritic spine morphology by SAP102 splice variants. J Neurosci 2011; 31: 89–96.
Gambrill AC, Barria A NMDA receptor subunit composition controls synaptogenesis and synapse stabilization. Proc Natl Acad Sci U S A 2011; 108: 5855–60.
Keith RE, Wild GA, Keith MJ, Chen D, Pack S, Dumas TC Individual NMDA receptor GluN2 subunit signaling domains differentially regulate the postnatal maturation of hippocampal excitatory synaptic transmission and plasticity but not dendritic morphology. Synapse 2024; 78: e22292.
Tian L, Stefanidakis M, Ning L, Van Lint P, Nyman-Huttunen H, Libert C, et al. Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage. J Cell Biol 2007; 178: 687–700.
Ultanir SK, Kim JE, Hall BJ, Deerinck T, Ellisman M, Ghosh A Regulation of spine morphology and spine density by NMDA receptor signaling in vivo. Proc Natl Acad Sci U S A 2007; 104: 19553–8.
Dalva MB, McClelland AC, Kayser MS Cell adhesion molecules: Signalling functions at the synapse. Nat Rev Neurosci 2007; 8: 206–20.
El-Husseini AE, Schnell E, Chetkovich DM, Nicoll RA, Bredt DS PSD-95 involvement in maturation of excitatory synapses. Science 2000; 290: 1364–8.
Yashiro K, Philpot BD Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity. Neuropharmacology 2008; 55: 1081–94.
Zhou Q, Homma KJ, Poo MM Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron 2004; 44: 749–57.
Chomczynski P, Sacchi N The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: Twenty-something years on. Nat Protoc 2006; 1: 581–5.
Pfaffl MW A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: e45.
Simonen M, Pedersen V, Weinmann O, Schnell L, Buss A, Ledermann B, et al. Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron 2003; 38: 201–11.
Fremeau RT Jr, Troyer MD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, et al. The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 2001; 31: 247–60.
Alonso-Nanclares L, Minelli A, Melone M, Edwards RH, Defelipe J, Conti F Perisomatic glutamatergic axon terminals: A novel feature of cortical synaptology revealed by vesicular glutamate transporter 1 immunostaining. Neuroscience 2004; 123: 547–56.
Cubelos B, Giménez C, Zafra F Localization of the GLYT1 glycine transporter at glutamatergic synapses in the rat brain. Cereb Cortex 2005; 15: 448–59.
Kubota Y, Hatada S, Kondo S, Karube F, Kawaguchi Y Neocortical inhibitory terminals innervate dendritic spines targeted by thalamocortical afferents. J Neurosci 2007; 27: 1139–50.
Melone M, Burette A, Weinberg RJ Light microscopic identification and immunocytochemical characterization of glutamatergic synapses in brain sections. J Comp Neurol 2005; 492: 495–509.
Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 2007; 318: 71–6.
Fournier AE, GrandPre T, Strittmatter SM Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 2001; 409: 341–6.
Dimou L, Schnell L, Montani L, Duncan C, Simonen M, Schneider R, et al. Nogo-A-deficient mice reveal strain-dependent differences in axonal regeneration. J Neurosci 2006; 26: 5591–603.
Montani L, Gerrits B, Gehrig P, Kempf A, Dimou L, Wollscheid B, et al. Neuronal Nogo-A modulates growth cone motility via Rho-GTP/LIMK1/cofilin in the unlesioned adult nervous system. J Biol Chem 2009; 284: 10793–807.
Caroni P, Schwab ME Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988; 106: 1281–8.
Caroni P, Schwab ME Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1988; 1: 85–96.
GrandPré T, Nakamura F, Vartanian T, Strittmatter SM Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 2000; 403: 439–44.
Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, et al. Inhibitor of neurite outgrowth in humans. Nature 2000; 403: 383–4.
Kempf A, Tews B, Arzt ME, Weinmann O, Obermair FJ, Pernet V, et al. The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. PLoS Biol 2014; 12: e1001763.
Lindau NT, Bänninger BJ, Gullo M, Good NA, Bachmann LC, Starkey ML, et al. Rewiring of the corticospinal tract in the adult rat after unilateral stroke and anti-Nogo-A therapy. Brain 2014; 137: 739–56.
Papadopoulos CM, Tsai SY, Cheatwood JL, Bollnow MR, Kolb BE, Schwab ME, et al. Dendritic plasticity in the adult rat following middle cerebral artery occlusion and Nogo-A neutralization. Cereb Cortex 2006; 16: 529–36.
Berry S, Weinmann O, Fritz AK, Rust R, Wolfer D, Schwab ME, et al. Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits. PLoS One 2018; 13: e0200896.
Craveiro LM, Hakkoum D, Weinmann O, Montani L, Stoppini L, Schwab ME Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice cultures. Eur J Neurosci 2008; 28: 1808–24.
Zagrebelsky M, Schweigreiter R, Bandtlow CE, Schwab ME, Korte M Nogo-A stabilizes the architecture of hippocampal neurons. J Neurosci 2010; 30: 13220–34.
Peng X, Kim J, Zhou Z, Fink DJ, Mata M Neuronal Nogo-A regulates glutamate receptor subunit expression in hippocampal neurons. J Neurochem 2011; 119: 1183–93.
Corson J, Nahmani M, Lubarsky K, Badr N, Wright C, Erisir A Sensory activity differentially modulates N-methyl-D-aspartate receptor subunits 2A and 2B in cortical layers. Neuroscience 2009; 163: 920–32.
Fu Z, Logan SM, Vicini S Deletion of the NR2A subunit prevents developmental changes of NMDA-mEPSCs in cultured mouse cerebellar granule neurones. J Physiol 2005; 563: 867–81.
Giza CC, Maria NS, Hovda DA N-methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. J Neurotrauma 2006; 23: 950–61.
Liu XB, Murray KD, Jones EG Switching of NMDA receptor 2A and 2B subunits at thalamic and cortical synapses during early postnatal development. J Neurosci 2004; 24: 8885–95.
Tang YP, Wang H, Feng R, Kyin M, Tsien JZ Differential effects of enrichment on learning and memory function in NR2B transgenic mice. Neuropharmacology 2001; 41: 779–90.
Kaneko T Local connections of excitatory neurons in motor-associated cortical areas of the rat. Front Neural Circuits 2013; 7: 75.
Huang S, Li Y, Zhang W, Zhang B, Liu X, Mo L, et al. Multisensory competition is modulated by sensory pathway interactions with fronto-sensorimotor and default-mode network regions. J Neurosci 2015; 35: 9064–77.
Yu J, Anderson CT, Kiritani T, Sheets PL, Wokosin DL, Wood L, et al. Local-circuit phenotypes of layer 5 neurons in motor-frontal cortex of YFP-H mice. Front Neural Circuits 2008; 2: 6.
Pernet V, Joly S, Dalkara D, Schwarz O, Christ F, Schaffer D, et al. Neuronal Nogo-A upregulation does not contribute to ER stress-associated apoptosis but participates in the regenerative response in the axotomized adult retina. Cell Death Differ 2012; 19: 1096–108.
Vajda F, Jordi N, Dalkara D, Joly S, Christ F, Tews B, et al. Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve. Cell Death Differ 2015; 22: 323–35.
Chang LR, Liu JP, Zhang N, Wang YJ, Gao XL, Wu Y Different expression of NR2B and PSD-95 in rat hippocampal subregions during postnatal development. Microsc Res Tech 2009; 72: 517–24.
Blanpied TA, Kerr JM, Ehlers MD Structural plasticity with preserved topology in the postsynaptic protein network. Proc Natl Acad Sci U S A 2008; 105: 12587–92.