Abstract
HSP70 are molecular chaperones that are present in neuronal cells, acting in cytoprotection and thermotolerance, preventing inflammation, apoptosis and cell death. It can be induced by a variety of stressful insults, but also by synaptic activity. Many physiological stimuli that induce long-term potentiation are also capable of stimulating the synthesis of HSP70. It’s induction is enhanced in the hippocampus after learning, during memory consolidation window, which is correlated to the animal performance and not the stress induced by the task. It is also induced markedly surround the synapses between the Shaffer collateral and pyramidal cells of the hippocampal CA1 region, a crucial structure involved in associative learning. Infusion of exogenous HSP70 facilitates memory consolidation through modulation of MAPK family activity in the hippocampus. HSP70 has been shown to be important in memory-related processes and can be quickly induced after training, indicating that memory is being mastered. Thus, it may be considered useful to be used as a learning index and also has a great potential as a pharmacological target to treat memory impairments. This chapter briefly reviews recent advances in our understanding of the role of HSP70 in synaptic plasticity and memory consolidation.
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Abbreviations
- 17-AAG:
-
17-N-allylamino-17-deethoxyglydanamycin
- AD:
-
Alzheimer’s disease
- AMPA:
-
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- BDNF:
-
brain-derived neurotrophic factor
- CAMKIV:
-
calcium and calmodulin dependent protein kinase IV
- CAMKII:
-
calcium and calmodulin dependent protein kinase II
- cAMP:
-
cyclic adenosine monophosphate
- CFC:
-
context fear conditioning
- CFTR:
-
cystic fibrosis transmembrane conductance regulator
- CNS:
-
central nervous system
- CRE:
-
cAMP responsive element
- ERK:
-
extracellular signal regulated kinase
- GluR:
-
glutamate receptor
- HSF:
-
heat hock factor
- HSP:
-
heat shock proteins
- JNK:
-
c-Jun NH (2) -terminal kinase
- LTD:
-
long-term depression
- LTP:
-
Long-term potentiation
- MAPK:
-
mitogen-activated protein kinase
- NF-κB:
-
nuclear factor κappa B
- NGF:
-
neuronal growth factor
- NMDA:
-
N-methyl D-aspartate
- p-ERK:
-
phosphorylated extracellular signal regulated kinase
- p-JNK:
-
c-Jun NH (2) -terminal phosphorylated kinase
- PKA:
-
protein kinase A
- PKB:
-
protein kinase B
- PKC:
-
protein kinase C
- PTSD:
-
post-traumatic stress disorder
- rHSP70:
-
recombinant 70 kDa heat shock protein
- SNARE:
-
N-ethylmaleimide soluble factor receptor binding protein
- SRE:
-
serum response element
- TLR:
-
toll like receptor
References
Abel T, Lattal KM (2001) Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol 11(2):180–187
Alberini CM, Milekic MH, Tronel S (2006) Mechanisms of memory stabilization and de-stabilization. Cell Mol Life Sci 63(9):999–1008. https://doi.org/10.1007/s00018-006-6025-7
Alonso M, Bevilaqua LR, Izquierdo I, Medina JH, Cammarota M (2003) Memory formation requires p38MAPK activity in the rat hippocampus. Neuroreport 14(15):1989–1992. https://doi.org/10.1097/01.wnr.0000091129.97039.f6
Ambrosini MV, Mariucci G, Tantucci M, Bruschelli G, Giuditta A (1999) Induction of cerebellar hsp72 in rats learning a two-way active avoidance task. Brain Res Mol Brain Res 70(1):164–166
Ambrosini MV, Mariucci G, Tantucci M, Van Hooijdonk L, Ammassari-Teule M (2005) Hippocampal 72-kDa heat shock protein expression varies according to mice learning performance independently from chronic exposure to stress. Hippocampus 15(4):413–417
Ammon-Treiber S, Grecksch G, Angelidis C, Vezyraki P, Höllt V, Becker A (2008) Emotional and learning behaviour in mice overexpressing heat shock protein 70. Neurobiol Learn Mem 90(2):358–364. https://doi.org/10.1016/j.nlm.2008.04.006
Bechtold DA, Brown IR (2000) Heat shock proteins Hsp27 and Hsp32 localize to synaptic sites in the rat cerebellum following hyperthermia. Brain Res Mol Brain Res 75(2):309–320
Bechtold DA, Rush SJ, Brown IR (2000) Localization of the heat-shock protein Hsp70 to the synapse following hyperthermic stress in the brain. J Neurochem 74(2):641–646
Belay HT, Brown IR (2006) Cell death and expression of heat-shock protein Hsc70 in the hyperthermic rat brain. J Neurochem 97(Suppl 1):116–119. https://doi.org/10.1111/j.1471-4159.2005.03591.x
Bertaina-Anglade V, Tramu G, Destrade C (2000) Differential learning-stage dependent patterns of c-Fos protein expression in brain regions during the acquisition and memory consolidation of an operant task in mice. Eur J Neurosci 12(10):3803–3812
Bobkova NV, Garbuz DG, Nesterova I, Medvinskaya N, Samokhin A, Alexandrova I et al (2014) Therapeutic effect of exogenous hsp70 in mouse models of Alzheimer’s disease. J Alzheimers Dis 38(2):425–435. https://doi.org/10.3233/JAD-130779
Calderwood SK (2007) Heat shock proteins in extracellular signaling. Methods 43(3):167. https://doi.org/10.1016/j.ymeth.2007.09.004
Casagrande MA, Haubrich J, Pedraza LK, Popik B, Quillfeldt JA, de Oliveira Alvares L (2018) Synaptic consolidation as a temporally variable process: Uncovering the parameters modulating its time-course. Neurobiol Learn Mem 150:42–47. https://doi.org/10.1016/j.nlm.2018.03.002
Chan SH, Chang KF, Ou CC, Chan JY (2002) Up-regulation of glutamate receptors in nucleus tractus solitarii underlies potentiation of baroreceptor reflex by heat shock protein 70. Mol Pharmacol 61(5):1097–1104
Chen Y, Wang B, Liu D, Li JJ, Xue Y, Sakata K et al (2014) Hsp90 chaperone inhibitor 17-AAG attenuates Aβ-induced synaptic toxicity and memory impairment. J Neurosci 34(7):2464–2470. https://doi.org/10.1523/JNEUROSCI.0151-13.2014
Chen ZC, Wu WS, Lin MT, Hsu CC (2009) Protective effect of transgenic expression of porcine heat shock protein 70 on hypothalamic ischemic and oxidative damage in a mouse model of heatstroke. BMC Neurosci 10:111. https://doi.org/10.1186/1471-2202-10-111
Choi HS, Li B, Lin Z, Huang E, Liu AY (1991) cAMP and cAMP-dependent protein kinase regulate the human heat shock protein 70 gene promoter activity. J Biol Chem 266(18):11858–11865
Chow AM, Brown IR (2007) Induction of heat shock proteins in differentiated human and rodent neurons by celastrol. Cell Stress Chaperones 12(3):237–244
De Maio A (2011) Extracellular heat shock proteins, cellular export vesicles, and the Stress Observation System: a form of communication during injury, infection, and cell damage. It is never known how far a controversial finding will go! Dedicated to Ferruccio Ritossa. Cell Stress Chaperones 16(3):235–249. https://doi.org/10.1007/s12192-010-0236-4
Eales KL, Palygin O, O’Loughlin T, Rasooli-Nejad S, Gaestel M, Müller J et al (2014) The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nat Commun 5:4701. https://doi.org/10.1038/ncomms5701
Ekimova IV, Nitsinskaya LE, Romanova IV, Pastukhov YF, Margulis BA, Guzhova IV (2010) Exogenous protein Hsp70/Hsc70 can penetrate into brain structures and attenuate the severity of chemically-induced seizures. J Neurochem 115(4):1035–1044. https://doi.org/10.1111/j.1471-4159.2010.06989.x
Foster JA, Brown IR (1996) Intracellular localization of heat shock mRNAs (hsc70 and hsp70) to neural cell bodies and processes in the control and hyperthermic rabbit brain. J Neurosci Res 46(6):652–665. https://doi.org/10.1002/(SICI)1097-4547(19961215)46:6<652::AID-JNR2>3.0.CO;2-E
Gabai VL, Meriin AB, Mosser DD, Caron AW, Rits S, Shifrin VI, Sherman MY (1997) Hsp70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance. J Biol Chem 272(29):18033–18037
Gabai VL, Meriin AB, Yaglom JA, Volloch VZ, Sherman MY (1998) Role of Hsp70 in regulation of stress-kinase JNK: implications in apoptosis and aging. FEBS Lett 438(1–2):1–4
Guzhova I, Kislyakova K, Moskaliova O, Fridlanskaya I, Tytell M, Cheetham M, Margulis B (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res 914(1–2):66–73
Guzhova IV, Arnholdt AC, Darieva ZA, Kinev AV, Lasunskaia EB, Nilsson K et al (1998) Effects of exogenous stress protein 70 on the functional properties of human promonocytes through binding to cell surface and internalization. Cell Stress Chaperones 3(1):67–77
Hung CH, Lin MT, Liao JF, Wang JJ (2004) Scopolamine-induced amnesia can be prevented by heat shock pretreatment in rats. Neurosci Lett 364(2):63–66. https://doi.org/10.1016/j.neulet.2004.02.074
Igaz LM, Bekinschtein P, Izquierdo I, Medina JH (2004) One-trial aversive learning induces late changes in hippocampal CaMKIIalpha, Homer 1a, Syntaxin 1a and ERK2 protein levels. Brain Res Mol Brain Res 132(1):1–12. https://doi.org/10.1016/j.molbrainres.2004.08.016
Izquierdo I, Bevilaqua LR, Rossato JI, Bonini JS, Medina JH, Cammarota M (2006) Different molecular cascades in different sites of the brain control memory consolidation. Trends Neurosci 29(9):496–505. https://doi.org/10.1016/j.tins.2006.07.005
Johansen JP, Cain CK, Ostroff LE, LeDoux JE (2011) Molecular mechanisms of fear learning and memory. Cell 147(3):509–524. https://doi.org/10.1016/j.cell.2011.10.009
Kandel ER (2012) The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 5:14. https://doi.org/10.1186/1756-6606-5-14
Kaneko M, Abe K, Kogure K, Saito H, Matsuki N (1993) Correlation between electroconvulsive seizure and HSC70 mRNA induction in mice brain. Neurosci Lett 157(2):195–198
Karunanithi S, Barclay JW, Brown IR, Robertson RM, Atwood HL (2002) Enhancement of presynaptic performance in transgenic Drosophila overexpressing heat shock protein Hsp70. Synapse 44(1):8–14. https://doi.org/10.1002/syn.10048
Kasza Á, Hunya Á, Frank Z, Fülöp F, Török Z, Balogh G et al (2016) Dihydropyridine Derivatives Modulate Heat Shock Responses and have a Neuroprotective Effect in a Transgenic Mouse Model of Alzheimer’s Disease. J Alzheimers Dis 53(2):557–571. https://doi.org/10.3233/JAD-150860
Lee JE, Yenari MA, Sun GH, Xu L, Emond MR, Cheng D et al (2001) Differential neuroprotection from human heat shock protein 70 overexpression in in vitro and in vivo models of ischemia and ischemia-like conditions. Exp Neurol 170(1):129–139. https://doi.org/10.1006/exnr.2000.7614
Lin YW, Yang HW, Min MY, Chiu TH (2004) Heat-shock pretreatment prevents suppression of long-term potentiation induced by scopolamine in rat hippocampal CA1 synapses. Brain Res 999(2):222–226. https://doi.org/10.1016/j.brainres.2003.11.057
Loones MT, Chang Y, Morange M (2000) The distribution of heat shock proteins in the nervous system of the unstressed mouse embryo suggests a role in neuronal and non-neuronal differentiation. Cell Stress Chaperones 5(4):291–305
Lu TZ, Quan Y, Feng ZP (2010) Multifaceted role of heat shock protein 70 in neurons. Mol Neurobiol 42(2):114–123. https://doi.org/10.1007/s12035-010-8116-6
McGaugh JL (2000) Memory--a century of consolidation. Science 287(5451):248–251
Mokrushin AA, Pavlinova LI, Plekhanov AY (2005) Heat shock protein HSP70 increases the resistance of cortical cells to glutamate excitotoxicity. Bull Exp Biol Med 140(1):1–5
Money TG, Anstey ML, Robertson RM (2005) Heat stress-mediated plasticity in a locust looming-sensitive visual interneuron. J Neurophysiol 93(4):1908–1919. https://doi.org/10.1152/jn.00908.2004
Morrison-Bogorad M, Pardue S, McIntire DD, Miller EK (1994) Cell size and the heat-shock response in rat brain. J Neurochem 63(3):857–867
Moser EI, Krobert KA, Moser MB, Morris RG (1998) Impaired spatial learning after saturation of long-term potentiation. Science 281(5385):2038–2042
Muller GE, Pilzecker A (1900) Experimentelle Beitra¨ge zur Lehre vom Geda¨chtnis. Z Psychol Erga¨nzungsband 1:1–300
Murshid A, Chou SD, Prince T, Zhang Y, Bharti A, Calderwood SK (2010) Protein kinase A binds and activates heat shock factor 1. PLoS One 5(11):e13830. https://doi.org/10.1371/journal.pone.0013830
Nedivi E, Hevroni D, Naot D, Israeli D, Citri Y (1993) Numerous candidate plasticity-related genes revealed by differential cDNA cloning. Nature 363(6431):718–722. https://doi.org/10.1038/363718a0
Nishimura RN, Dwyer BE (1996) Evidence for different mechanisms of induction of HSP70i: a comparison of cultured rat cortical neurons with astrocytes. Brain Res Mol Brain Res 36(2):227–239
O’Dell TJ, Kandel ER, Grant SG (1991) Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors. Nature 353(6344):558–560. https://doi.org/10.1038/353558a0
Ortega L, Calvillo M, Luna F, Pérez-Severiano F, Rubio-Osornio M, Guevara J, Limón ID (2014) 17-AAG improves cognitive process and increases heat shock protein response in a model lesion with Aβ25-35. Neuropeptides 48(4):221–232. https://doi.org/10.1016/j.npep.2014.04.006
Pavlik A, Aneja IS, Lexa J, Al-Zoabi BA (2003) Identification of cerebral neurons and glial cell types inducing heat shock protein Hsp70 following heat stress in the rat. Brain Res 973(2):179–189
Pizarro JM, Haro LS, Barea-Rodriguez EJ (2003) Learning associated increase in heat shock cognate 70 mRNA and protein expression. Neurobiol Learn Mem 79(2):142–151
Porto RR, Dutra FD, Crestani AP, Holsinger RMD, Quillfeldt JA, Homem de Bittencourt PI, de Oliveira Alvares L (2018) HSP70 Facilitates Memory Consolidation of Fear Conditioning through MAPK Pathway in the Hippocampus. Neuroscience 375:108–118. https://doi.org/10.1016/j.neuroscience.2018.01.028
Price BD, Calderwood SK (1991) Ca2+ is essential for multistep activation of the heat shock factor in permeabilized cells. Mol Cell Biol 11(6):3365–3368
Rao A, Steward O (1991) Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: analysis of proteins synthesized within synaptosomes. J Neurosci 11(9):2881–2895
Schafe GE, Nader K, Blair HT, LeDoux JE (2001) Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective. Trends Neurosci 24(9):540–546
Seger R, Krebs EG (1995) The MAPK signaling cascade. FASEB J 9(9):726–735
Sheller RA, Smyers ME, Grossfeld RM, Ballinger ML, Bittner GD (1998) Heat-shock proteins in axoplasm: high constitutive levels and transfer of inducible isoforms from glia. J Comp Neurol 396(1):1–11
Sherrin T, Blank T, Hippel C, Rayner M, Davis RJ, Todorovic C (2010) Hippocampal c-Jun-N-terminal kinases serve as negative regulators of associative learning. J Neurosci 30(40):13348–13361. https://doi.org/10.1523/JNEUROSCI.3492-10.2010
Sherrin T, Blank T, Todorovic C (2011) c-Jun N-terminal kinases in memory and synaptic plasticity. Rev Neurosci 22(4):403–410. https://doi.org/10.1515/RNS.2011.032
Song I, Kamboj S, Xia J, Dong H, Liao D, Huganir RL (1998) Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21(2):393–400
Sunada H, Riaz H, de Freitas E, Lukowiak K, Swinton C, Swinton E et al (2016) Heat stress enhances LTM formation in Lymnaea: role of HSPs and DNA methylation. J Exp Biol 219(Pt 9):1337–1345. https://doi.org/10.1242/jeb.134296
Suzuki A, Fukushima H, Mukawa T, Toyoda H, Wu LJ, Zhao MG et al (2011) Upregulation of CREB-mediated transcription enhances both short- and long-term memory. J Neurosci 31(24):8786–8802. https://doi.org/10.1523/JNEUROSCI.3257-10.2011
Suzuki T, Usuda N, Murata S, Nakazawa A, Ohtsuka K, Takagi H (1999) Presence of molecular chaperones, heat shock cognate (Hsc) 70 and heat shock proteins (Hsp) 40, in the postsynaptic structures of rat brain. Brain Res 816(1):99–110
Swayne LA, Beck KE, Braun JE (2006) The cysteine string protein multimeric complex. Biochem Biophys Res Commun 348(1):83–91. https://doi.org/10.1016/j.bbrc.2006.07.033
Taylor DM, De Koninck P, Minotti S, Durham HD (2007) Manipulation of protein kinases reveals different mechanisms for upregulation of heat shock proteins in motor neurons and non-neuronal cells. Mol Cell Neurosci 34(1):20–33. https://doi.org/10.1016/j.mcn.2006.09.007
Teskey ML, Lukowiak KS, Riaz H, Dalesman S, Lukowiak K (2012) What’s hot: the enhancing effects of thermal stress on long-term memory formation in Lymnaea stagnalis. J Exp Biol 215(Pt 24):4322–4329. https://doi.org/10.1242/jeb.075960
Thomas GM, Huganir RL (2004) MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 5(3):173–183. https://doi.org/10.1038/nrn1346
Thomas GM, Lin DT, Nuriya M, Huganir RL (2008) Rapid and bi-directional regulation of AMPA receptor phosphorylation and trafficking by JNK. EMBO J 27(2):361–372. https://doi.org/10.1038/sj.emboj.7601969
Tong L, Prieto GA, Kramar EA, Smith ED, Cribbs DH, Lynch G, Cotman CW (2012) Brain-derived neurotrophic factor-dependent synaptic plasticity is suppressed by Interleukin-1 via p38 mitogen-activated protein kinase. J Neurosci 32(49):17714–17724
Ungewickell E, Ungewickell H, Holstein SE, Lindner R, Prasad K, Barouch W et al (1995) Role of auxilin in uncoating clathrin-coated vesicles. Nature 378(6557):632–635. https://doi.org/10.1038/378632a0
Visvader J, Sassone-Corsi P, Verma IM (1988) Two adjacent promoter elements mediate nerve growth factor activation of the c-fos gene and bind distinct nuclear complexes. Proc Natl Acad Sci U S A 85(24):9474–9478
Walker PD, Carlock LR (1993) Timing the excitotoxic induction of heat shock protein 70 transcription. Neuroreport 4(6):699–702
Wang Q, Walsh DM, Rowan MJ, Selkoe DJ, Anwyl R (2004) Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J Neurosci 24(13):3370–3378. https://doi.org/10.1523/JNEUROSCI.1633-03.2004
Xiong W, Kojic LZ, Zhang L, Prasad SS, Douglas R, Wang Y, Cynader MS (2006) Anisomycin activates p38 MAP kinase to induce LTD in mouse primary visual cortex. Brain Res 1085(1):68–76. https://doi.org/10.1016/j.brainres.2006.02.015
Xu L, Giffard RG (1997) HSP70 protects murine astrocytes from glucose deprivation injury. Neurosci Lett 224(1):9–12
Yang Y, Janich S, Cohn JA, Wilson JM (1993) The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. Proc Natl Acad Sci U S A 90(20):9480–9484
Yao S, Peng M, Zhu X, Cheng M, Qi X (2007) Heat shock protein72 protects hippocampal neurons from apoptosis induced by chronic psychological stress. Int J Neurosci 117(11):1551–1564. https://doi.org/10.1080/00207450701239285
Young JC (2014) The role of the cytosolic HSP70 chaperone system in diseases caused by misfolding and aberrant trafficking of ion channels. Dis Model Mech 7(3):319–329. https://doi.org/10.1242/dmm.014001
Zheng Z, Kim JY, Ma H, Lee JE, Yenari MA (2008) Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke. J Cereb Blood Flow Metab 28(1):53–63. https://doi.org/10.1038/sj.jcbfm.9600502
Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R (2002) Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 110(4):443–455
Zhu Y, Pak D, Qin Y, McCormack SG, Kim MJ, Baumgart JP et al (2005) Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron 46(6):905–916. https://doi.org/10.1016/j.neuron.2005.04.037
Acknowledgements
The authors thank the Neuroscience Post-Graduate Program from the Federal University of Rio Grande do Sul (UFRGS). This work was supported in part by CAPES and PROPESQ (UFRGS).
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Porto, R.R., de Oliveira Alvares, L. (2019). Role of HSP70 in Plasticity and Memory. In: Asea, A., Kaur, P. (eds) Heat Shock Proteins in Neuroscience. Heat Shock Proteins, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-030-24285-5_5
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