Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

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

Mini-Review Article

Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration

Author(s): Khalid Saad Alharbi, Waleed Hassan Almalki, Sami I. Alzarea, Imran Kazmi, Fahad A. Al-Abbasi, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Mohammed Albratty, Asim Najmi and Gaurav Gupta*

Volume 23, Issue 4, 2024

Published on: 06 June, 2023

Page: [411 - 419] Pages: 9

DOI: 10.2174/1871527322666230508123558

Price: $65

Abstract

General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochemical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that require continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.

Keywords: General anaesthetics, γ-aminobutyric acid A (GABAA) receptor agonist, neurodegenerative disorders, Aβ plaqueassociated Alzheimer's disease, long-term potentiation, depression.

Next »
Graphical Abstract
[1]
Lee E, Lee J, Kim E. Excitation/inhibition imbalance in animal models of autism spectrum disorders. Biol Psychiatry 2017; 81(10): 838-47.
[http://dx.doi.org/10.1016/j.biopsych.2016.05.011] [PMID: 27450033]
[2]
Meredith RM. Sensitive and critical periods during neurotypical and aberrant neurodevelopment: A framework for neurodevelopmental disorders. Neurosci Biobehav Rev 2015; 50: 180-8.
[http://dx.doi.org/10.1016/j.neubiorev.2014.12.001] [PMID: 25496903]
[3]
Ikonomidou C, Bittigau P, Ishimaru MJ, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 2000; 287(5455): 1056-60.
[http://dx.doi.org/10.1126/science.287.5455.1056] [PMID: 10669420]
[4]
Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999; 283(5398): 70-4.
[http://dx.doi.org/10.1126/science.283.5398.70] [PMID: 9872743]
[5]
Ju LS, Yang JJ, Morey TE, et al. Role of epigenetic mechanisms in transmitting the effects of neonatal sevoflurane exposure to the next generation of male, but not female, rats. Br J Anaesth 2018; 121(2): 406-16.
[http://dx.doi.org/10.1016/j.bja.2018.04.034] [PMID: 30032879]
[6]
Palanisamy A, Baxter MG, Keel PK, Xie Z, Crosby G, Culley DJ. Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults. Anesthesiology 2011; 114(3): 521-8.
[http://dx.doi.org/10.1097/ALN.0b013e318209aa71] [PMID: 21307768]
[7]
Dalla Massara L, Osuru HP, Oklopcic A, et al. General anesthesia causes epigenetic histone modulation of c-fos and brain-derived neurotrophic factor, target genes important for neuronal development in the immature rat hippocampus. Anesthesiology 2016; 124(6): 1311-27.
[http://dx.doi.org/10.1097/ALN.0000000000001111] [PMID: 27028464]
[8]
Ju LS, Yang JJ, Xu N, et al. Intergenerational effects of sevoflurane in young adult rats. Anesthesiology 2019; 131(5): 1092-109.
[http://dx.doi.org/10.1097/ALN.0000000000002920] [PMID: 31517640]
[9]
Yu D, Huang LJ, Chen NM. Anesthetic propofol-induced gene expression changes in patients undergoing coronary artery bypass graft surgery based on dynamical differential coexpression network analysis. Comput Math Methods Med 2016; 2016: 1-8.
[http://dx.doi.org/10.1155/2016/7097612] [PMID: 27437027]
[10]
Kotani N, Hashimoto H, Sessler DI, et al. Expression of genes for proinflammatory cytokines in alveolar macrophages during propofol and isoflurane anesthesia. Anesth Analg 1999; 89(5): 1250-6.
[http://dx.doi.org/10.1213/00000539-199911000-00032] [PMID: 10553845]
[11]
Wu Z, Zhao P. Epigenetic alterations in anesthesia-induced neurotoxicity in the developing brain. Front Physiol 2018; 9: 1024.
[http://dx.doi.org/10.3389/fphys.2018.01024] [PMID: 30108514]
[12]
Krauss BS, Krauss BA, Green SM. Videos in clinical medicine. Procedural sedation and analgesia in children. N Engl J Med 2014; 370(15): e23.
[http://dx.doi.org/10.1056/NEJMvcm1108559] [PMID: 24716701]
[13]
Chidambaran V, Costandi A, D’Mello A. Propofol: A review of its role in pediatric anesthesia and sedation. CNS Drugs 2015; 29(7): 543-63.
[http://dx.doi.org/10.1007/s40263-015-0259-6] [PMID: 26290263]
[14]
Marik P. Propofol: Therapeutic indications and side-effects. Curr Pharm Des 2004; 10(29): 3639-49.
[http://dx.doi.org/10.2174/1381612043382846] [PMID: 15579060]
[15]
Cravero JP, Beach ML, Blike GT, Gallagher SM, Hertzog JH. The incidence and nature of adverse events during pediatric sedation/anesthesia with propofol for procedures outside the operating room: A report from the Pediatric Sedation Research Consortium. Anesth Analg 2009; 108(3): 795-804.
[http://dx.doi.org/10.1213/ane.0b013e31818fc334] [PMID: 19224786]
[16]
Thal SC, Timaru-Kast R, Wilde F, et al. Propofol impairs neurogenesis and neurologic recovery and increases mortality rate in adult rats after traumatic brain injury. Crit Care Med 2014; 42(1): 129-41.
[http://dx.doi.org/10.1097/CCM.0b013e3182a639fd] [PMID: 24126440]
[17]
Davies C. Excitatory phenomena following the use of propofol in dogs. Vet Anaesth Analg 1991; 18: 48-51.
[18]
Doyon N, Vinay L, Prescott SA, De Koninck Y. Chloride regulation: A dynamic equilibrium crucial for synaptic inhibition. Neuron 2016; 89(6): 1157-72.
[http://dx.doi.org/10.1016/j.neuron.2016.02.030] [PMID: 26985723]
[19]
Yelhekar TD, Druzin M, Johansson S. Contribution of resting conductance, GABA(A)-receptor mediated miniature synaptic currents and neurosteroid to chloride homeostasis in central neurons. eNeuro 2017; 4(2): ENEURO.0019-.
[20]
Rivera C, Voipio J, Payne JA, et al. The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 1999; 397(6716): 251-5.
[http://dx.doi.org/10.1038/16697] [PMID: 9930699]
[21]
Murata Y, Colonnese MT. GABAergic interneurons excite neonatal hippocampus in vivo. Sci Adv 2020; 6(24): eaba1430.
[http://dx.doi.org/10.1126/sciadv.aba1430] [PMID: 32582852]
[22]
Kfir A, Awasthi R, Ghosh S, et al. A cellular mechanism of learning-induced enhancement of synaptic inhibition: PKC-Dependent upregulation of KCC2 activation. Sci Rep 2020; 10(1): 962.
[http://dx.doi.org/10.1038/s41598-020-57626-2] [PMID: 31969605]
[23]
Moody EJ, Harris BD, Skolnick P. Stereospecific actions of the inhalation anesthetic isoflurane at the GABAA receptor complex. Brain Res 1993; 615(1): 101-6.
[http://dx.doi.org/10.1016/0006-8993(93)91119-D] [PMID: 8395953]
[24]
Orser BA, Wang LY, Pennefather PS, MacDonald JF. Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J Neurosci 1994; 14(12): 7747-60.
[http://dx.doi.org/10.1523/JNEUROSCI.14-12-07747.1994] [PMID: 7996209]
[25]
Jones MV, Harrison NL. Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons. J Neurophysiol 1993; 70(4): 1339-49.
[http://dx.doi.org/10.1152/jn.1993.70.4.1339] [PMID: 7506753]
[26]
Imperato A, Dazzi L, Obinu MC, Gessa GL, Biggio G. Inhibition of hippocampal acetylcholine release by benzodiazepines: Antagonism by flumazenil. Eur J Pharmacol 1993; 238(1): 135-7.
[http://dx.doi.org/10.1016/0014-2999(93)90518-M] [PMID: 8405078]
[27]
Walder B, Tramèr MR, Seeck M. Seizure-like phenomena and propofol: A systematic review. Neurology 2002; 58(9): 1327-32.
[http://dx.doi.org/10.1212/WNL.58.9.1327] [PMID: 12017156]
[28]
Conn PJ, Pin JP. Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 1997; 37(1): 205-37.
[http://dx.doi.org/10.1146/annurev.pharmtox.37.1.205] [PMID: 9131252]
[29]
Mayat E, Petralia RS, Wang YX, Wenthold RJ. Immunoprecipitation, immunoblotting, and immunocytochemistry studies suggest that glutamate receptor delta subunits form novel postsynaptic receptor complexes. J Neurosci 1995; 15(3): 2533-46.
[http://dx.doi.org/10.1523/JNEUROSCI.15-03-02533.1995] [PMID: 7891187]
[30]
Zuo J, De Jager PL, Takahashi KA, Jiang W, Linden DJ, Heintz N. Neurodegeneration in Lurcher mice caused by mutation in δ2 glutamate receptor gene. Nature 1997; 388(6644): 769-73.
[http://dx.doi.org/10.1038/42009] [PMID: 9285588]
[31]
Ikeno K, Yamakura T, Yamazaki M, Sakimura K. The Lurcher mutation reveals Ca2+ permeability and PKC modification of the GluRδ channels. Neurosci Res 2001; 41(2): 193-200.
[http://dx.doi.org/10.1016/S0168-0102(01)00277-2] [PMID: 11591446]
[32]
Partin KM, Patneau DK, Winters CA, Mayer ML, Buonanno A. Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron 1993; 11(6): 1069-82.
[http://dx.doi.org/10.1016/0896-6273(93)90220-L] [PMID: 7506043]
[33]
Kohda K, Wang Y, Yuzaki M. Mutation of a glutamate receptor motif reveals its role in gating and δ2 receptor channel properties. Nat Neurosci 2000; 3(4): 315-22.
[http://dx.doi.org/10.1038/73877] [PMID: 10725919]
[34]
Partin KM, Bowie D, Mayer ML. Structural determinants of allosteric regulation in alternatively spliced AMPA receptors. Neuron 1995; 14(4): 833-43.
[http://dx.doi.org/10.1016/0896-6273(95)90227-9] [PMID: 7718245]
[35]
Paoletti P, Ascher P, Neyton J. High-affinity zinc inhibition of NMDA NR1-NR2A receptors. J Neurosci 1997; 17(15): 5711-25.
[http://dx.doi.org/10.1523/JNEUROSCI.17-15-05711.1997] [PMID: 9221770]
[36]
Hansen KB, Yi F, Perszyk RE, et al. Structure, function, and allosteric modulation of NMDA receptors. J Gen Physiol 2018; 150(8): 1081-105.
[http://dx.doi.org/10.1085/jgp.201812032] [PMID: 30037851]
[37]
Izquterdo I. Pharmacological evidence for a role of long‐term potentiation in memory. FASEB J 1994; 8(14): 1139-45.
[http://dx.doi.org/10.1096/fasebj.8.14.7958619] [PMID: 7958619]
[38]
Rockstroh S, Emre M, Pokorny R, Tarral A. Effects of the novel NMDA-receptor antagonist SDZ EAA 494 on memory and attention in humans. Psychopharmacology 1996; 124(3): 261-6.
[http://dx.doi.org/10.1007/BF02246666] [PMID: 8740048]
[39]
Bashir ZI, Alford S, Davies SN, Randall AD, Collingridge GL. Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature 1991; 349(6305): 156-8.
[http://dx.doi.org/10.1038/349156a0] [PMID: 1846031]
[40]
Muller D, Lynch G. Long-term potentiation differentially affects two components of synaptic responses in hippocampus. Proc Natl Acad Sci 1988; 85(23): 9346-50.
[http://dx.doi.org/10.1073/pnas.85.23.9346] [PMID: 2904150]
[41]
Selig DK, Hjelmstad GO, Herron C, Nicoll RA, Malenka RC. Independent mechanisms for long-term depression of AMPA and NMDA responses. Neuron 1995; 15(2): 417-26.
[http://dx.doi.org/10.1016/0896-6273(95)90045-4] [PMID: 7544143]
[42]
Volianskis A, France G, Jensen MS, Bortolotto ZA, Jane DE, Collingridge GL. Long-term potentiation and the role of N -methyl- d -aspartate receptors. Brain Res 2015; 1621: 5-16.
[http://dx.doi.org/10.1016/j.brainres.2015.01.016] [PMID: 25619552]
[43]
Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity: Impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci 2013; 14(6): 383-400.
[http://dx.doi.org/10.1038/nrn3504] [PMID: 23686171]
[44]
Jentsch JD, Roth RH. The neuropsychopharmacology of phencyclidine: From NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1999; 20: 201-25.
[45]
Izquierdo I, Medina JH. Role of the amygdala, hippocampus and entorhinal cortex in memory consolidation and expression, Brazilian journal of medical and biological research =. Rev Bras Pesqui Med Biol 1993; 26: 573-89.
[46]
Morris RGM, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 1986; 319(6056): 774-6.
[http://dx.doi.org/10.1038/319774a0] [PMID: 2869411]
[47]
Fletcher PC, Honey GD. Schizophrenia, ketamine and cannabis: Evidence of overlapping memory deficits. Trends Cogn Sci 2006; 10(4): 167-74.
[http://dx.doi.org/10.1016/j.tics.2006.02.008] [PMID: 16531099]
[48]
Lee JLC, Everitt BJ. Appetitive memory reconsolidation depends upon NMDA receptor-mediated neurotransmission. Neurobiol Learn Mem 2008; 90(1): 147-54.
[http://dx.doi.org/10.1016/j.nlm.2008.02.004] [PMID: 18372198]
[49]
Morris RGM, Garrud P, Rawlins JNP, O’Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature 1982; 297(5868): 681-3.
[http://dx.doi.org/10.1038/297681a0] [PMID: 7088155]
[50]
Liu F, Paule MG, Ali S, Wang C. Ketamine-induced neurotoxicity and changes in gene expression in the developing rat brain. Curr Neuropharmacol 2011; 9(1): 256-61.
[http://dx.doi.org/10.2174/157015911795017155] [PMID: 21886601]
[51]
Loepke AW, Soriano SG. An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function. Anesth Analg 2008; 106(6): 1681-707.
[http://dx.doi.org/10.1213/ane.0b013e318167ad77] [PMID: 18499597]
[52]
Loepke AW, Istaphanous GK, McAuliffe JJ III, et al. The effects of neonatal isoflurane exposure in mice on brain cell viability, adult behavior, learning, and memory. Anesth Analg 2009; 108(1): 90-104.
[http://dx.doi.org/10.1213/ane.0b013e31818cdb29] [PMID: 19095836]
[53]
Johnson SA, Young C, Olney JW. Isoflurane-induced neuroapoptosis in the developing brain of nonhypoglycemic mice. J Neurosurg Anesthesiol 2008; 20(1): 21-8.
[http://dx.doi.org/10.1097/ANA.0b013e3181271850] [PMID: 18157021]
[54]
Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003; 23(3): 876-82.
[http://dx.doi.org/10.1523/JNEUROSCI.23-03-00876.2003] [PMID: 12574416]
[55]
Wang HY, Eguchi K, Yamashita T, Takahashi T. Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. J Neurosci 2020; 40(21): 4103-15.
[http://dx.doi.org/10.1523/JNEUROSCI.2946-19.2020] [PMID: 32327530]
[56]
Baumgart JP, Zhou ZY, Hara M, et al. Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca 2+ influx, not Ca 2+ -exocytosis coupling. Proc Natl Acad Sci 2015; 112(38): 11959-64.
[http://dx.doi.org/10.1073/pnas.1500525112] [PMID: 26351670]
[57]
Liang G, Wang Q, Li Y, et al. A presenilin-1 mutation renders neurons vulnerable to isoflurane toxicity. Anesth Analg 2008; 106(2): 492-500.
[http://dx.doi.org/10.1213/ane.0b013e3181605b71] [PMID: 18227305]
[58]
Yang H, Liang G, Hawkins BJ, Madesh M, Pierwola A, Wei H. Inhalational anesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies. Anesthesiology 2008; 109(2): 243-50.
[http://dx.doi.org/10.1097/ALN.0b013e31817f5c47] [PMID: 18648233]
[59]
Wei H, Liang G, Yang H, et al. The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors. Anesthesiology 2008; 108(2): 251-60.
[http://dx.doi.org/10.1097/01.anes.0000299435.59242.0e] [PMID: 18212570]
[60]
Xie Z, Culley DJ, Dong Y, et al. The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid β-protein level in vivo. Ann Neurol 2008; 64(6): 618-27.
[http://dx.doi.org/10.1002/ana.21548] [PMID: 19006075]
[61]
Bianchi SL, Tran T, Liu C, et al. Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 2008; 29(7): 1002-10.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.02.009] [PMID: 17346857]
[62]
Roderic G, Jonas SJ, Huafeng W. Anesthetic enhancement of amyloid-β oligomerization and cytotoxicity, anesthesiology. Anesthesiology 2004; 101: 703-9.
[63]
Upton DH, Popovic K, Fulton R, Kassiou M. Anaesthetic-dependent changes in gene expression following acute and chronic exposure in the rodent brain. Sci Rep 2020; 10(1): 9366.
[http://dx.doi.org/10.1038/s41598-020-66122-6] [PMID: 32518252]
[64]
Aho V, Ollila HM, Rantanen V, et al. Partial sleep restriction activates immune response-related gene expression pathways: experimental and epidemiological studies in humans. PLoS One 2013; 8(10): e77184-4.
[http://dx.doi.org/10.1371/journal.pone.0077184] [PMID: 24194869]
[65]
Livingstone RW, Elder MK, Barrett MC, et al. Secreted amyloid precursor protein-alpha promotes arc protein synthesis in hippocampal neurons. Front Mol Neurosci 2019; 12: 198.
[http://dx.doi.org/10.3389/fnmol.2019.00198] [PMID: 31474829]
[66]
Gómez RM, Rosso OA, Berretta R, Moscato P. Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus’ gene expression profiles in Alzheimer’s disease. PLoS One 2010; 5(4): e10153.
[http://dx.doi.org/10.1371/journal.pone.0010153] [PMID: 20405009]
[67]
Yin Z, Raj D, Saiepour N, et al. Immune hyperreactivity of Aβ plaque-associated microglia in Alzheimer’s disease. Neurobiol Aging 2017; 55: 115-22.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.03.021] [PMID: 28434692]
[68]
Stetler R, Gao Y, Signore A, Cao G, Chen J. HSP27: Mechanisms of cellular protection against neuronal injury. Curr Mol Med 2009; 9(7): 863-72.
[http://dx.doi.org/10.2174/156652409789105561] [PMID: 19860665]
[69]
Milbrandt J. Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene. Neuron 1988; 1(3): 183-8.
[http://dx.doi.org/10.1016/0896-6273(88)90138-9] [PMID: 3272167]
[70]
Law SW, Conneely OM, DeMayo FJ, O’Malley BW. Identification of a new brain-specific transcription factor, NURR1. Mol Endocrinol 1992; 6(12): 2129-35.
[PMID: 1491694]
[71]
Ohkura N, Hijikuro M, Yamamoto A, Miki K. Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells. Biochem Biophys Res Commun 1994; 205(3): 1959-65.
[http://dx.doi.org/10.1006/bbrc.1994.2900] [PMID: 7811288]
[72]
Docagne F, Nicole O, Gabriel C, et al. Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-beta 1 against NMDA-induced necrosis. Mol Cell Neurosci 2002; 21(4): 634-44.
[http://dx.doi.org/10.1006/mcne.2002.1206] [PMID: 12504596]
[73]
Nagai N, Suzuki Y, Van Hoef B, Lijnen HR, Collen D. Effects of plasminogen activator inhibitor-1 on ischemic brain injury in permanent and thrombotic middle cerebral artery occlusion models in mice. J Thromb Haemost 2005; 3(7): 1379-84.
[http://dx.doi.org/10.1111/j.1538-7836.2005.01466.x] [PMID: 15978095]
[74]
Jeong JY, Lee DH, Kang SS. Effects of chronic restraint stress on body weight, food intake, and hypothalamic gene expressions in mice. Endocrinol Metab 2013; 28(4): 288-96.
[http://dx.doi.org/10.3803/EnM.2013.28.4.288] [PMID: 24396694]
[75]
Gamaro G, Manoli LP, Torres ILS, Silveira R, Dalmaz C. Effects of chronic variate stress on feeding behavior and on monoamine levels in different rat brain structures. Neurochem Int 2003; 42(2): 107-14.
[http://dx.doi.org/10.1016/S0197-0186(02)00080-3] [PMID: 12421590]
[76]
Leung H-W, Foo GWQ, VanDongen AMJ. Arc regulates transcription of genes for plasticity, excitability and Alzheimer’s Disease bioRxiv 2019; 833988.
[http://dx.doi.org/10.1101/833988]
[77]
Gonzales BJ, Mukherjee D, Ashwal-Fluss R, Loewenstein Y, Citri A. Subregion-specific rules govern the distribution of neuronal immediate-early gene induction. Proc Natl Acad Sci 2019; 117(38): 23304-10.
[78]
Poirier R, Cheval H, Mailhes C, Charnay P, Davis S, Laroche S. Paradoxical role of an Egr transcription factor family member, Egr2/Krox20, in learning and memory. Front Behav Neurosci 2007; 1: 6-6.
[http://dx.doi.org/10.3389/neuro.08.006.2007] [PMID: 18958188]
[79]
McNulty SE, Barrett RM, Vogel-Ciernia A, et al. Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory. Learn Mem 2012; 19(12): 588-92.
[http://dx.doi.org/10.1101/lm.026385.112] [PMID: 23161447]
[80]
Zhang Y, Chen G, Gao B, et al. NR4A1 knockdown suppresses seizure activity by regulating surface expression of NR2B. Sci Rep 2016; 6(1): 37713-3.
[http://dx.doi.org/10.1038/srep37713] [PMID: 27876882]
[81]
Lei X, Guo Q, Zhang J. Mechanistic insights into neurotoxicity induced by anesthetics in the developing brain. Int J Mol Sci 2012; 13(6): 6772-99.
[http://dx.doi.org/10.3390/ijms13066772] [PMID: 22837663]

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