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General Review Article

The Effects of P75NTR on Learning Memory Mediated by Hippocampal Apoptosis and Synaptic Plasticity

Author(s): Jun-Jie Tang, Shuang Feng, Xing-Dong Chen, Hua Huang, Min Mao, Hai-Yan Wang, Sen Li, Xiu-Min Lu* and Yong-Tang Wang*

Volume 27, Issue 4, 2021

Published on: 16 September, 2020

Page: [531 - 539] Pages: 9

DOI: 10.2174/1381612826666200916145142

Price: $65

Abstract

Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its proapoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or proapoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

Keywords: Nervous system diseases, learning and memory, hippocampus, apoptosis, synaptic plasticity, P75NTR signaling.

« Previous Next »
[1]
Becker K, Cana A, Baumgärtner W, Spitzbarth I. p75 Neurotrophin Receptor: A double-edged sword in pathology and regeneration of the central nervous system. Vet Pathol 2018; 55(6): 786-801.
[http://dx.doi.org/10.1177/0300985818781930] [PMID: 29940812]
[2]
Elshaer SL, El-Remessy AB. Deletion of p75NTR prevents vaso-obliteration and retinal neovascularization via activation of Trk- A receptor in ischemic retinopathy model. Sci Rep 2018; 8(1): 12490.
[http://dx.doi.org/10.1038/s41598-018-30029-0] [PMID: 30131506]
[3]
Donnelly CR, Gabreski NA, Suh EB, Chowdhury M, Pierchala BA. Non-canonical Ret signaling augments p75-mediated cell death in developing sympathetic neurons. J Cell Biol 2018; 217(9): 3237-53.
[http://dx.doi.org/10.1083/jcb.201703120] [PMID: 30018091]
[4]
Sakuragi S, Tominaga-Yoshino K, Ogura A. Involvement of TrkB- and p75(NTR)-signaling pathways in two contrasting forms of long-lasting synaptic plasticity. Sci Rep 2013; 3: 3185.
[http://dx.doi.org/10.1038/srep03185] [PMID: 24212565]
[5]
Notaras M, van den Buuse M. Brain-derived neurotrophic factor (BDNF): Novel insights into regulation and genetic variation. Neuroscientist 2019; 25(5): 434-54.
[http://dx.doi.org/10.1177/1073858418810142] [PMID: 30387693]
[6]
Suelves N, Miguez A, López-Benito S, et al. Early Downregulation of p75NTR by Genetic and Pharmacological Approaches Delays the Onset of Motor Deficits and Striatal Dysfunction in Huntington’s Disease Mice. Mol Neurobiol 2019; 56(2): 935-53.
[http://dx.doi.org/10.1007/s12035-018-1126-5] [PMID: 29804232]
[7]
Kisiswa L, Fernández-Suárez D, Sergaki MC, Ibáñez CF. RIP2 gates TRAF6 interaction with death receptor p75(NTR) to regulate cerebellar granule neuron survival. Cell Rep 2018; 24(4): 1013-24.
[http://dx.doi.org/10.1016/j.celrep.2018.06.098] [PMID: 30044969]
[8]
Zagrebelsky M, Holz A, Dechant G, Barde YA, Bonhoeffer T, Korte M. The p75 neurotrophin receptor negatively modulates dendrite complexity and spine density in hippocampal neurons. J Neurosci 2005; 25(43): 9989-99.
[http://dx.doi.org/10.1523/JNEUROSCI.2492-05.2005] [PMID: 16251447]
[9]
Theotokis P, Grigoriadis N. p75NTR and TROY: Uncharted roles of Nogo receptor complex in experimental autoimmune encephalomyelitis. Mol Neurobiol 2018; 55(8): 6329-36.
[http://dx.doi.org/10.1007/s12035-017-0841-7] [PMID: 29294247]
[10]
Delbary-Gossart S, Lee S, Baroni M, et al. A novel inhibitor of p75-neurotrophin receptor improves functional outcomes in two models of traumatic brain injury. Brain 2016; 139(Pt 6): 1762-82.
[http://dx.doi.org/10.1093/brain/aww074] [PMID: 27084575]
[11]
Fujii T, Kunugi H. p75NTR as a therapeutic target for neuropsychiatric diseases. Curr Mol Pharmacol 2009; 2(1): 70-6.
[http://dx.doi.org/10.2174/1874467210902010070] [PMID: 20021447]
[12]
Tanaka K, Kelly CE, Goh KY, Lim KB, Ibáñez CF. Death domain signaling by disulfide-linked dimers of the p75 neurotrophin receptor mediates neuronal death in the CNS. J Neurosci 2016; 36(20): 5587-95.
[http://dx.doi.org/10.1523/JNEUROSCI.4536-15.2016] [PMID: 27194337]
[13]
Yuan W, Ibáñez CF, Lin Z. Death domain of p75 neurotrophin receptor: a structural perspective on an intracellular signalling hub. Biol Rev Camb Philos Soc 2019; 94(4): 1282-93.
[http://dx.doi.org/10.1111/brv.12502] [PMID: 30762293]
[14]
Bono F, Lamarche I, Bornia J, Savi P, Della Valle G, Herbert JM. Nerve growth factor (NGF) exerts its pro-apoptotic effect via the P75NTR receptor in a cell cycle-dependent manner. FEBS Lett 1999; 457(1): 93-7.
[http://dx.doi.org/10.1016/S0014-5793(99)01006-6] [PMID: 10486571]
[15]
Fahnestock M, Shekari A. ProNGF and neurodegeneration in Alzheimer’s disease. Front Neurosci 2019; 13: 129.
[http://dx.doi.org/10.3389/fnins.2019.00129] [PMID: 30853882]
[16]
Zhang H, Zhang C, Vincent J, et al. Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington’s disease models. Nat Commun 2018; 9(1): 4272.
[http://dx.doi.org/10.1038/s41467-018-06675-3] [PMID: 30323233]
[17]
He M, Wei JX, Mao M, et al. Synaptic plasticity in PTSD and associated comorbidities: the function and mechanism for diagnostics and therapy. Curr Pharm Des 2018; 24(34): 4051-9.
[http://dx.doi.org/10.2174/1381612824666181120094749] [PMID: 30457048]
[18]
Penn AC, Zhang CL, Georges F, et al. Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors. Nature 2017; 549(7672): 384-8.
[http://dx.doi.org/10.1038/nature23658] [PMID: 28902836]
[19]
Dong Z, Bai Y, Wu X, et al. Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze. Neuropharmacology 2013; 64: 65-73.
[http://dx.doi.org/10.1016/j.neuropharm.2012.06.027] [PMID: 22732443]
[20]
Sheng N, Bemben MA, Díaz-Alonso J, Tao W, Shi YS, Nicoll RA. LTP requires postsynaptic PDZ-domain interactions with glutamate receptor/auxiliary protein complexes. Proc Natl Acad Sci USA 2018; 115(15): 3948-53.
[http://dx.doi.org/10.1073/pnas.1800719115] [PMID: 29581259]
[21]
McLeod F, Bossio A, Marzo A, et al. Wnt signaling mediates LTP-dependent spine plasticity and AMPAR localization through frizzled-7 receptors. Cell Rep 2018; 23(4): 1060-71.
[http://dx.doi.org/10.1016/j.celrep.2018.03.119] [PMID: 29694885]
[22]
Pérez V, Bermedo-Garcia F, Zelada D, et al. The p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability. Acta Neuropathol Commun 2019; 7(1): 147.
[http://dx.doi.org/10.1186/s40478-019-0802-7] [PMID: 31514753]
[23]
Rösch H, Schweigreiter R, Bonhoeffer T, Barde YA, Korte M. The neurotrophin receptor p75NTR modulates long-term depression and regulates the expression of AMPA receptor subunits in the hippocampus. Proc Natl Acad Sci USA 2005; 102(20): 7362-7.
[http://dx.doi.org/10.1073/pnas.0502460102] [PMID: 15883381]
[24]
Woo NH, Teng HK, Siao CJ, et al. Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 2005; 8(8): 1069-77.
[http://dx.doi.org/10.1038/nn1510] [PMID: 16025106]
[25]
Lu XM, Wei JX, Xiao L, Shu YH, Wang YT. Experimental and clinical advances in immunotherapy strategies for spinal cord injury target on MAIs and their receptors. Curr Pharm Des 2016; 22(6): 728-37.
[http://dx.doi.org/10.2174/1381612822666151204000855] [PMID: 26635269]
[26]
Shu YH, Lu XM, Wei JX, Xiao L, Wang YT. Update on the role of p75NTR in neurological disorders: A novel therapeutic target. Biomed Pharmacother 2015; 76: 17-23.
[http://dx.doi.org/10.1016/j.biopha.2015.10.010] [PMID: 26653545]
[27]
Atwal JK, Pinkston-Gosse J, Syken J, et al. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 2008; 322(5903): 967-70.
[http://dx.doi.org/10.1126/science.1161151] [PMID: 18988857]
[28]
Fujita Y, Takashima R, Endo S, Takai T, Yamashita T. The p75 receptor mediates axon growth inhibition through an association with PIR-B. Cell Death Dis 2011; 2e198
[http://dx.doi.org/10.1038/cddis.2011.85] [PMID: 21881600]
[29]
Bisbal M, Remedi M, Quassollo G, Cáceres A, Sanchez M. Rotenone inhibits axonogenesis via an Lfc/RhoA/ROCK pathway in cultured hippocampal neurons. J Neurochem 2018; 146(5): 570-84.
[http://dx.doi.org/10.1111/jnc.14547] [PMID: 29972689]
[30]
Schilling JM, Kassan A, Mandyam C, et al. Inhibition of p75 neurotrophin receptor does not rescue cognitive impairment in adulthood after isoflurane exposure in neonatal mice. Br J Anaesth 2017; 119(3): 465-71.
[http://dx.doi.org/10.1093/bja/aew299] [PMID: 28969308]
[31]
Yang C, Li T, Xue H, et al. Inhibition of necroptosis rescues SAH-induced synaptic impairments in hippocampus via CREB-BDNF pathway. Front Neurosci 2019; 12: 990.
[http://dx.doi.org/10.3389/fnins.2018.00990] [PMID: 30666179]
[32]
Düsedau HP, Kleveman J, Figueiredo CA, et al. p75NTR regulates brain mononuclear cell function and neuronal structure in Toxoplasma infection-induced neuroinflammation. Glia 2019; 67(1): 193-211.
[http://dx.doi.org/10.1002/glia.23553] [PMID: 30597659]
[33]
Miguez A, García-Díaz Barriga G, Brito V, et al. Fingolimod (FTY720) enhances hippocampal synaptic plasticity and memory in Huntington’s disease by preventing p75NTR up-regulation and astrocyte-mediated inflammation. Hum Mol Genet 2015; 24(17): 4958-70.
[http://dx.doi.org/10.1093/hmg/ddv218] [PMID: 26063761]
[34]
Seo SW, Thibodeau MP, Perry DC, et al. Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration. Neurology 2018; 90(12): e1047-56.
[http://dx.doi.org/10.1212/WNL.0000000000005163] [PMID: 29453245]
[35]
Shen LL, Mañucat-Tan NB, Gao SH, et al. The ProNGF/p75NTR pathway induces tau pathology and is a therapeutic target for FTLD-tau. Mol Psychiatry 2018; 23(8): 1813-24.
[http://dx.doi.org/10.1038/s41380-018-0071-z] [PMID: 29867188]
[36]
Galimberti D, Fenoglio C, Serpente M, et al. Autosomal dominant frontotemporal lobar degeneration due to the C9ORF72 hexanucleotide repeat expansion: late-onset psychotic clinical presentation. Biol Psychiatry 2013; 74(5): 384-91.
[http://dx.doi.org/10.1016/j.biopsych.2013.01.031] [PMID: 23473366]
[37]
Park JH, Ju YH, Choi JW, et al. Newly developed reversible MAO-B inhibitor circumvents the shortcomings of irreversible inhibitors in Alzheimer’s disease. Sci Adv 2019; 5(3)eaav0316
[http://dx.doi.org/10.1126/sciadv.aav0316] [PMID: 30906861]
[38]
Bogie J, Hoeks C, Schepers M, et al. Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer’s disease mouse model. Sci Rep 2019; 9(1): 4908.
[http://dx.doi.org/10.1038/s41598-019-41399-4] [PMID: 30894635]
[39]
Zhong L, Xu Y, Zhuo R, et al. Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model. Nat Commun 2019; 10(1): 1365.
[http://dx.doi.org/10.1038/s41467-019-09118-9] [PMID: 30911003]
[40]
Yao XQ, Jiao SS, Saadipour K, et al. p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer’s disease. Mol Psychiatry 2015; 20(11): 1301-10.
[http://dx.doi.org/10.1038/mp.2015.49] [PMID: 25917367]
[41]
Xu Y, Li WW, Wang J, et al. Neurotrophin receptor p75 mRNA level in peripheral blood cells of patients with Alzheimer’s disease. Neurotox Res 2019; 36(1): 101-7.
[http://dx.doi.org/10.1007/s12640-019-00035-9] [PMID: 30977102]
[42]
Couly S, Paucard A, Bonneaud N, et al. Improvement of BDNF signalling by P42 peptide in Huntington’s disease. Hum Mol Genet 2018; 27(17): 3012-28.
[http://dx.doi.org/10.1093/hmg/ddy207] [PMID: 29860423]
[43]
Dargaei Z, Liang X, Serranilla M, Santos J, Woodin MA. Alterations in hippocampal inhibitory synaptic transmission in the R6/2 mouse model of Huntington’s disease. Neuroscience 2019; 404: 130-40.
[http://dx.doi.org/10.1016/j.neuroscience.2019.02.007] [PMID: 30797895]
[44]
Brito V, Giralt A, Enriquez-Barreto L, et al. Neurotrophin receptor p75(NTR) mediates Huntington’s disease-associated synaptic and memory dysfunction. J Clin Invest 2014; 124(10): 4411-28.
[http://dx.doi.org/10.1172/JCI74809] [PMID: 25180603]
[45]
Wecht JM, Weir JP, Katzelnick CG, et al. Systemic and cerebral hemodynamic contribution to cognitive performance in spinal cord injury. J Neurotrauma 2018; 35(24): 2957-64.
[http://dx.doi.org/10.1089/neu.2018.5760] [PMID: 30113243]
[46]
Grau JW, Huang YJ, Turtle JD, et al. When pain hurts: Nociceptive stimulation induces a state of maladaptive plasticity and impairs recovery after spinal cord injury. J Neurotrauma 2017; 34(10): 1873-90.
[http://dx.doi.org/10.1089/neu.2016.4626] [PMID: 27788626]
[47]
Tan AM, Stamboulian S, Chang YW, et al. Neuropathic pain memory is maintained by Rac1-regulated dendritic spine remodeling after spinal cord injury. J Neurosci 2008; 28(49): 13173-83.
[http://dx.doi.org/10.1523/JNEUROSCI.3142-08.2008] [PMID: 19052208]
[48]
Tep C, Lim TH, Ko PO, et al. Oral administration of a small molecule targeted to block proNGF binding to p75 promotes myelin sparing and functional recovery after spinal cord injury. J Neurosci 2013; 33(2): 397-410.
[http://dx.doi.org/10.1523/JNEUROSCI.0399-12.2013] [PMID: 23303920]
[49]
Jure I, Pietranera L, De Nicola AF, Labombarda F. Spinal cord injury impairs neurogenesis and induces glial reactivity in the hippocampus. Neurochem Res 2017; 42(8): 2178-90.
[http://dx.doi.org/10.1007/s11064-017-2225-9] [PMID: 28290135]
[50]
Wu J, Stoica BA, Luo T, et al. Isolated spinal cord contusion in rats induces chronic brain neuroinflammation, neurodegeneration, and cognitive impairment. Involvement of cell cycle activation. Cell Cycle 2014; 13(15): 2446-58.
[http://dx.doi.org/10.4161/cc.29420] [PMID: 25483194]
[51]
Sullivan DR, Marx B, Chen MS, Depue BE, Hayes SM, Hayes JP. Behavioral and neural correlates of memory suppression in PTSD. J Psychiatr Res 2019; 112: 30-7.
[http://dx.doi.org/10.1016/j.jpsychires.2019.02.015] [PMID: 30844595]
[52]
Collingridge GL, Peineau S, Howland JG, Wang YT. Long-term depression in the CNS. Nat Rev Neurosci 2010; 11(7): 459-73.
[http://dx.doi.org/10.1038/nrn2867] [PMID: 20559335]

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