Skip to main content

Advertisement

SpringerLink
Log in

Pharmacological Manipulation of Trk, p75NTR, and NGF Balance Restores Memory Deficit in Global Ischemia/Reperfusion Model in Rats

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Long-term memory impairment is reported in more than 50% of cardiac arrest survivors. Monosialoganglioside (GM1) provided neuroprotection in experimental models of stroke but failed to replicate its promise clinically for unknown reasons. GM1 stimulates the release of nerve growth factor (NGF), which is synthesized as a precursor protein (pro-NGF) that either mediates apoptosis through the p75 neurotrophin receptor (p75NTR) or is cleaved by the protease furin (FUR) to yield mature NGF, the latter supporting survival through tropomyosin kinase receptor (Trk). The flavanol epicatechin (EPI) inhibits p75NTR-mediated signaling and apoptosis by pro-NGF. The aim of the current work is to test whether these two drugs affect, or communicate with, each other in the setting of CNS injuries. Using the two-vessel occlusion model of global ischemia/reperfusion (I/R), we tested if pharmacological modulation of Trk, p75NTR, and NGF balance with GM1, EPI, and their combination, can correct the memory deficit that follows this insult. Finally, we tested if FUR insufficiency and/or p75NTR-mediated apoptosis negatively affect the neurotherapeutic effect of GM1. Key proteins for Trk and p75NTR, FUR, and both forms of NGF were assessed. All treatment regiments successfully improved spatial memory retention and acquisition. A week after the insult, most Trk and p75NTR proteins were normal, but pro/mature NGF ratio remained sharply elevated and was associated with the poorest memory performance. Pharmacological correction of this balance was achieved by reinforcing Trk and p75NTR signaling. GM1 increased FUR levels, while concomitant administration of EPI weakened GM1 effect on pro-survival Trk and p75NTR mediators. GM1 neuroprotection is therefore not limited by FUR but could be dependent on p75NTR.

"."

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

Akt:

Protein kinase B

Bcl-2:

B cell lymphoma-2 protein

CA:

Cardiac arrest

CT:

Cycle threshold

DMSO:

Dimethyl sulfoxide

EPI:

Epicatechin

FUR:

Furin

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GM1:

Monosialoganglioside

GSK3β:

Glycogen synthase kinase 3β

I/R:

Ischemia/reperfusion

JNK:

Jun-kinase

MCAO:

Middle cerebral artery occlusion

NF- κB:

Nuclear factor-κB

NGF:

Nerve growth factor

NTs:

Neurotrophins

p38MAPK:

Mitogen-activated protein kinase

p75NTR:

p75 neurotrophin receptor

PI3K:

Phosphoinositol-3 kinase

PLC:

Phospholipase-C

PTEN:

phosphatase and tensin homolog

Trk:

Tropomyosin kinase receptor

References

  • Al-Gayyar MM, Matragoon S, Pillai BA, Ali TK, Abdelsaid MA, El-Remessy AB (2011) Epicatechin blocks pro-nerve growth factor (proNGF)-mediated retinal neurodegeneration via inhibition of p75 neurotrophin receptor expression in a rat model of diabetes [corrected]. Diabetologia 54:669–680

    Article  CAS  PubMed  Google Scholar 

  • Aloe L, Rocco ML, Bianchi P, Manni L (2012) Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med 10:239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alter M (1998) GM1 ganglioside for acute ischemic stroke. Trial design issues. Ann N Y Acad Sci 845:391–401

    Article  CAS  PubMed  Google Scholar 

  • Angelo MF, Aviles-Reyes RX, Villarreal A, Barker P, Reines AG, Ramos AJ (2009) p75 NTR expression is induced in isolated neurons of the penumbra after ischemia by cortical devascularization. J Neurosci Res 87:1892–1903

    Article  CAS  PubMed  Google Scholar 

  • Atkins CM, Oliva AA Jr, Alonso OF, Pearse DD, Bramlett HM, Dietrich WD (2007) Modulation of the cAMP signaling pathway after traumatic brain injury. Exp Neurol 208:145–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beattie MS, Harrington AW, Lee R, Kim JY, Boyce SL, Longo FM, Bresnahan JC, Hempstead BL, Yoon SO (2002) ProNGF induces p75-mediated death of oligodendrocytes following spinal cord injury. Neuron 36:375–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brambrink AM, Schneider A, Noga H, Astheimer A, Gotz B, Korner I, Heimann A, Welschof M, Kempski O (2000) Tolerance-inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning. J Cereb Blood Flow Metab 20:1425–1436

    Article  CAS  PubMed  Google Scholar 

  • Broadbent NJ, Squire LR, Clark RE (2004) Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci U S A 101:14515–14520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Candelise L, Ciccone A (2002) Gangliosides for acute ischemic stroke. Stroke 33:2336

    Article  PubMed  Google Scholar 

  • Capsoni S, Brandi R, Arisi I, D'Onofrio M, Cattaneo A (2011) A dual mechanism linking NGF/proNGF imbalance and early inflammation to Alzheimer’s disease neurodegeneration in the AD11 anti-NGF mouse model. CNS Neurol Disord Drug Targets 10:635–647

    Article  CAS  PubMed  Google Scholar 

  • Carmack SA, Block CL, Howell KK, Anagnostaras SG (2014) Methylphenidate enhances acquisition and retention of spatial memory. Neurosci Lett 567:45–50

    Article  CAS  PubMed  Google Scholar 

  • Chao MV (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 4:299–309

    Article  CAS  PubMed  Google Scholar 

  • Chen T, Wang J, Li C, Zhang W, Zhang L, An L, Pang T, Shi X, Liao H (2014) Nafamostat mesilate attenuates neuronal damage in a rat model of transient focal cerebral ischemia through thrombin inhibition. Sci. Rep 4:5531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coucha M, Li W, Johnson MH, Fagan SC, Ergul A (2013) Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke. Am J Physiol Heart Circ Physiol 305:H1726–H1735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davies AM (1995) The Bcl-2 family of proteins, and the regulation of neuronal survival. Trends Neurosci 18:355–358

    Article  CAS  PubMed  Google Scholar 

  • Davies AM, Lee KF, Jaenisch R (1993) p75-deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins. Neuron 11:565–574

    Article  CAS  PubMed  Google Scholar 

  • De SE, Zazzeroni F, Papa S, Nguyen DU, Jin R, Jones J, Cong R, Franzoso G (2001) Induction of gadd45beta by NF-kappaB downregulates pro-apoptotic JNK signalling. Nature 414:308–313

    Article  Google Scholar 

  • Deblon N, Bourgoin L, Veyrat-Durebex C, Peyrou M, Vinciguerra M, Caillon A, Maeder C, Fournier M, Montet X, Rohner-Jeanrenaud F, Foti M (2012) Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br J Pharmacol 165:2325–2340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di PA, Maglione V, Alpaugh M, Horkey M, Atwal RS, Sassone J, Ciammola A, Steffan JS, Fouad K, Truant R, Sipione S (2012) Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice. Proc Natl Acad Sci U S A 109:3528–3533

    Article  Google Scholar 

  • Fong TG, Neff NH, Hadjiconstantinou M (1997) GM1 ganglioside improves spatial learning and memory of aged rats. Behav Brain Res 85:203–211

    Article  CAS  PubMed  Google Scholar 

  • Fujioka M, Nishio K, Miyamoto S, Hiramatsu KI, Sakaki T, Okuchi K, Taoka T, Fujioka S (2000) Hippocampal damage in the human brain after cardiac arrest. Cerebrovasc Dis 10:2–7

    Article  CAS  PubMed  Google Scholar 

  • Goold RG, Gordon-Weeks PR (2003) NGF activates the phosphorylation of MAP1B by GSK3beta through the TrkA receptor and not the p75(NTR) receptor. J Neurochem 87:935–946

    Article  CAS  PubMed  Google Scholar 

  • Hadjiconstantinou M, Neff NH (1998) GM1 ganglioside: in vivo and in vitro trophic actions on central neurotransmitter systems. J Neurochem:1335–1345

  • Harrington AW, Kim JY, Yoon SO (2002) Activation of Rac GTPase by p75 is necessary for c-jun N-terminal kinase-mediated apoptosis. J Neurosci 22:156–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrington AW, Leiner B, Blechschmitt C, Arevalo JC, Lee R, Morl K, Meyer M, Hempstead BL, Yoon SO, Giehl KM (2004) Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury. Proc Natl Acad Sci U S A 101:6226–6230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopkins CR, Gibson A, Shipman M, Miller K (1990) Movement of internalized ligand-receptor complexes along a continuous endosomal reticulum. Nature 346:335–339

    Article  CAS  PubMed  Google Scholar 

  • Horner PJ, Gage FH (2000) Regenerating the damaged central nervous system. Nature 407:963–970

    Article  CAS  PubMed  Google Scholar 

  • Irmady K, Jackman KA, Padow VA, Shahani N, Martin LA, Cerchietti L, Unsicker K, Iadecola C, Hempstead BL (2014) Mir-592 regulates the induction and cell death-promoting activity of p75NTR in neuronal ischemic injury. J Neurosci 34:3419–3428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Janis LS, Glasier MM, Stein DG (1997) Effects of a single intraseptal injection of NGF on spatial learning in the water maze. Physiol Behav 62:69–76

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Domon-Dell C, Kang J, Chung DH, Freund JN, Evers BM (2004) Down-regulation of the tumor suppressor PTEN by the tumor necrosis factor-alpha/nuclear factor-kappaB (NF-kappaB)-inducing kinase/NF-kappaB pathway is linked to a default IkappaB-alpha autoregulatory loop. J Biol Chem 279:4285–4291

    Article  CAS  PubMed  Google Scholar 

  • Kokaia Z, Andsberg G, Martinez-Serrano A, Lindvall O (1998) Focal cerebral ischemia in rats induces expression of P75 neurotrophin receptor in resistant striatal cholinergic neurons. Neuroscience 84:1113–1125

    Article  CAS  PubMed  Google Scholar 

  • Langnaese K, John R, Schweizer H, Ebmeyer U, Keilhoff G (2008) Selection of reference genes for quantitative real-time PCR in a rat asphyxial cardiac arrest model. BMC Mol Biol 9:53

  • Lazzaro A, Seren MS, Koga T, Zanoni R, Schiavo N, Manev H (1994) GM1 reduces infarct volume after focal cerebral ischemia. Exp Neurol 125:278–285

    Article  CAS  PubMed  Google Scholar 

  • Le AP, Friedman WJ (2012) Matrix metalloproteinase-7 regulates cleavage of pro-nerve growth factor and is neuroprotective following kainic acid-induced seizures. J Neurosci 32:703–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ledeen RW (1978) Ganglioside structures and distribution: are they localized at the nerve ending? J Supramol Struct 8:1–17

    Article  CAS  PubMed  Google Scholar 

  • Lee TH, Kato H, Chen ST, Kogure K, Itoyama Y (1998) Expression of nerve growth factor and trkA after transient focal cerebral ischemia in rats. Stroke 29:1687–1696

    Article  CAS  PubMed  Google Scholar 

  • Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294:1945–1948

    Article  CAS  PubMed  Google Scholar 

  • Lenzi GL, Grigoletto F, Gent M, Roberts RS, Walker MD, Easton JD, Carolei A, Dorsey FC, Rocca WA, Bruno R (1994) Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial. Stroke 25:1552–1558

    Article  CAS  PubMed  Google Scholar 

  • Leon A, Lipartiti M, Seren MS, Lazzaro A, Mazzari S, Koga T, Toffano G, Skaper SD (1990) Hypoxic-ischemic damage and the neuroprotective effects of GM1 ganglioside. Stroke 21:III95–III97

    CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Lu B, Pang PT, Woo NH (2005) The yin and yang of neurotrophin action. Nat Rev Neurosci 6:603–614

    Article  CAS  PubMed  Google Scholar 

  • Makkerh JP, Ceni C, Auld DS, Vaillancourt F, Dorval G, Barker PA (2005) p75 neurotrophin receptor reduces ligand-induced Trk receptor ubiquitination and delays Trk receptor internalization and degradation. EMBO Rep 6:936–941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mocchetti I (2005) Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins. Cell Mol Life Sci 62:2283–2294

    Article  CAS  PubMed  Google Scholar 

  • Moulaert VR, Verbunt JA, van Heugten CM, Wade DT (2009) Cognitive impairments in survivors of out-of-hospital cardiac arrest: a systematic review. Resuscitation 80:297–305

    Article  PubMed  Google Scholar 

  • Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER, III CSM, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB (2015) Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131:e29–e322

    PubMed  Google Scholar 

  • Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M (2002) Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 110:429–441

    Article  CAS  PubMed  Google Scholar 

  • Pan W, Banks WA, Kastin AJ (1998) Permeability of the blood-brain barrier to neurotrophins. Brain Res 788:87–94

    Article  CAS  PubMed  Google Scholar 

  • Rabin SJ, Mocchetti I (1995) GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem 65:347–354

    Article  CAS  PubMed  Google Scholar 

  • Rabin SJ, Bachis A, Mocchetti I (2002) Gangliosides activate Trk receptors by inducing the release of neurotrophins. J Biol Chem 277:49466–49472

    Article  CAS  PubMed  Google Scholar 

  • Reichardt LF (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 361:1545–1564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roux PP, Barker PA (2002) Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol 67:203–233

    Article  CAS  PubMed  Google Scholar 

  • S.a.T.F.o.t.A.H.A. ECC Committee (2005) American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 112:IV1–IV203

    Article  Google Scholar 

  • Sanderson TH, Reynolds CA, Kumar R, Przyklenk K, Huttemann M (2013) Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol 47:9–23

    Article  CAS  PubMed  Google Scholar 

  • Seif el NM, Nuglisch J, Krieglstein J (1992) Prevention of ischemia-induced cerebral hypothermia by controlling the environmental temperature. J Pharmacol Toxicol Methods 27:23–26

    Article  Google Scholar 

  • Shah ZA, Li RC, Ahmad AS, Kensler TW, Yamamoto M, Biswal S, Dore S (2010) The flavanol (-)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway. J Cereb Blood Flow Metab 30:1951–1961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soligo M, Protto V, Florenzano F, Bracci-Laudiero L, De Benedetti F, Chiaretti A, Manni L (2015) The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: analysis by ELISA methods. Brain Res 1624:455–468

    Article  CAS  PubMed  Google Scholar 

  • Song W, Volosin M, Cragnolini AB, Hempstead BL, Friedman WJ (2010) ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons. J Neurosci 30:15608–15615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sorkin A, Waters CM (1993) Endocytosis of growth factor receptors. Bioessays 15:375–382

    Article  CAS  PubMed  Google Scholar 

  • Takahashi Y, Shimokawa N, Esmaeili-Mahani S, Morita A, Masuda H, Iwasaki T, Tamura J, Haglund K, Koibuchi N (2011) Ligand-induced downregulation of TrkA is partly regulated through ubiquitination by Cbl. FEBS Lett 585:1741–1747

    Article  CAS  PubMed  Google Scholar 

  • Teng KK, Hempstead BL (2004) Neurotrophins and their receptors: signaling trios in complex biological systems. Cell Mol Life Sci 61:35–48

    Article  CAS  PubMed  Google Scholar 

  • Teng KK, Felice S, Kim T, Hempstead BL (2010) Understanding proneurotrophin actions: recent advances and challenges. Dev Neurobiol 70:350–359

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tiveron C, Fasulo L, Capsoni S, Malerba F, Marinelli S, Paoletti F, Piccinin S, Scardigli R, Amato G, Brandi R, Capelli P, D'Aguanno S, Florenzano F, La Regina F, Lecci A, Manca A, Meli G, Pistillo L, Berretta N, Nistico R, Pavone F, Cattaneo A (2013) ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice. Cell Death Differ 20:1017–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ulrich PT, Kroppenstedt S, Heimann A, Kempski O (1998) Laser-Doppler scanning of local cerebral blood flow and reserve capacity and testing of motor and memory functions in a chronic 2-vessel occlusion model in rats. Stroke 29:2412–2420

    Article  CAS  PubMed  Google Scholar 

  • van Praaq H, Lucero MJ, Yeo GW, Stecker K, Heivand N, Zhao C, Yip E, Afanador M, Schroeter H, Hammerstone J, Gage FH (2007) Plant-derived flavanol (−)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 27:5869–5878

    Article  CAS  Google Scholar 

  • Wadowska M, Woods J, Rogozinska M, Briones TL (2015) Neuroprotective effects of enriched environment housing after transient global cerebral ischaemia are associated with the upregulation of insulin-like growth factor-1 signalling. Neuropathol Appl Neurobiol 41:544–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waterman H, Yarden Y (2001) Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases. FEBS Lett 490:142–152

    Article  CAS  PubMed  Google Scholar 

  • Weber M, Mohand-Said S, Hicks D, Dreyfus H, Sahel JA (1996) Monosialoganglioside GM1 reduces ischemia--reperfusion-induced injury in the rat retina. Invest Ophthalmol Vis Sci 37:267–273

    CAS  PubMed  Google Scholar 

  • Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV (2011) Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Mol Neurodegener 6:11

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu C, Fujihara H, Yao J, Qi S, Li H, Shimoji K, Baba H (2003) Different expression patterns of Bcl-2, Bcl-xl, and Bax proteins after sublethal forebrain ischemia in C57Black/Crj6 mouse striatum. Stroke 34:1803–1808

    Article  CAS  PubMed  Google Scholar 

  • Xu R, Zhou Y, Fang X, Lu Y, Li J, Zhang J, Deng X, Li S (2014) The possible mechanism of Parkinson’s disease progressive damage and the preventive effect of GM1 in the rat model induced by 6-hydroxydopamine. Brain Res 1592:73–81

    Article  CAS  PubMed  Google Scholar 

  • Yoon SO, Casaccia-Bonnefil P, Carter B, Chao MV (1998) Competitive signaling between TrkA and p75 nerve growth factor receptors determines cell survival. J Neurosci 18:3273–3281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu C, Minemoto Y, Zhang J, Liu J, Tang F, Bui TN, Xiang J, Lin A (2004) JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Mol Cell 13:329–340

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini st., Cairo, 11562, Egypt

    Ali Mohamed Choucry, Muhammad Yusuf Al-Shorbagy & Hanan Salah El-Abhar

  2. Department of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, Toyama University, 2630 Sugitani, Toyama, 930-0194, Japan

    Ali Mohamed Choucry

  3. School of Pharmacy, New Giza University, Giza, Egypt

    Muhammad Yusuf Al-Shorbagy

  4. Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo, 11562, Egypt

    Ahmed Sherif Attia

Authors
  1. Ali Mohamed Choucry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muhammad Yusuf Al-Shorbagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed Sherif Attia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hanan Salah El-Abhar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.M.C. conceived the study. A.M.C. and H.S.E. jointly designed the experiments. A.M.C. performed the experiments. A.S.A. designed and supervised RT-PCR experiments. A.M.C. and A.S.A. jointly quantified and analyzed gene expression. A.M.C. and M.Y.A. isolated and preserved hippocampal tissue samples. A.M.C., M.Y.A., and H.S.E. performed the statistical analysis. A.M.C. and H.S.E. interpreted the data and wrote the article. M.Y.A. and A.S.A. provided technical support and reviewed the manuscript.

Corresponding author

Correspondence to Muhammad Yusuf Al-Shorbagy.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choucry, A.M., Al-Shorbagy, M.Y., Attia, A.S. et al. Pharmacological Manipulation of Trk, p75NTR, and NGF Balance Restores Memory Deficit in Global Ischemia/Reperfusion Model in Rats. J Mol Neurosci 68, 78–90 (2019). https://doi.org/10.1007/s12031-019-01284-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-019-01284-1

Keywords

Search

Navigation