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2004, Number 3

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Salud Mental 2004; 27 (3)

Understanding the neurobiological mechanisms of learning and memory: cellular, molecular and gene regulation implicated in synaptic plasticity and long-term potentiation. Part IVB

Pavón RL, Hernández ME, Loría SF, Sandoval LG

Language: English
References: 87
Page: 19-25
PDF size: 77.31 Kb.


ABSTRACT

For 20 years, a great number of clinical and experimental evidence have shown the existence of a constant and bi-directional communication between the neuroendocrine system and the immune response, called neuroendocrineimmune (NEI) interactions. These interactions help the homeostasis maintenance to stressful stimuli, whether they are physical or systemic bacterial, viral or parasitical infections, as well as tissular injuries or psychological stress, that is secondary to the individual’s perception and processing.
Stress is a physicochemical or emotional process that induces tension. This process promotes the release of proinflamatory cytokines, hormones such as the corticotrophin-release hormone (CRH) and cortisol, and a wide number of neurotransmitters that are together responsible for some behavioral alterations. Both systemic and psychological stress elicits an equivalent response in an organism, but acute stressors have effects considered beneficial, while chronic stressors have nocive effects.
The adaptative response of the organism to a stressful stimulus consists of an increase of the sera levels of proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukine (IL)-1 and IL-6, produced by immune response cells like the lymphocytes and macrophages. When this proinflammatory cytokines reach a 10nM concentration, they bind to their receptors and can stimulate the Central Nervous System (CNS). Although the brain has specific cytokine receptors located in different anatomical regions, the most densely one is the hippocampus. In addition to the existence of a great number of cytokine receptors in the brain, this organ has the capacity to synthesize and secrete in situ a wide variety of cytokines, ability that makes it susceptible of being stimulated by both systemic and in situ produced cytokines.
The activity of the NEI interactions starts when systemic or psychological stressful stimuli lead to the release of proinflammatory cytokines. When these reach a 10nM concentration, they bind to their specific brain receptors, following different neural pathways and a cascade of events is thus triggered: 1) Neuroimmune events initiate the cytokine release within the brain, 2) neurochemical events initiate the release of neurotransmitters, such as norepinephrine (NE) and serotonine (5HT), 3) neuroendocrine events beginning with CRH secretion activate the hipotalamus-pituitary-adrenal (HPA) axis. The activity of the axis finishes when cortisol and anabolic androgens, such as dehydroepiandrosterone (DHEA), are released into the blood stream. All the previous events lead ultimately to 4) behavioral changes known as “sickness behavior”.
Both cortisol and DHEA have specific receptors in almost every cell, particularly those of the immune response like the T lymphocytes, which are highly susceptible to variations in the circulating levels of these molecules. At low concentrations and during short periods of time, cortisol acts as an immunostimulant, especially for a T lymphocyte subset known as T-helper 2 (TH2), involved in the humoral immune response, mainly mediated by antibodies. On the other hand, DHEA positively stimulates the T lymphocyte subset called T-helper 1 (TH1), which favors the cellular immune response.
The difference between TH1 and TH2 lymphocyte subsets lies in the profile of cytokines secreted by each one. TH1 cells secrete proinflammatory cytokines, such as IL-1, TNF-α and IL-6, while TH2 cells secrete antinflammatory cytokines, such as IL-10, IL-13 and IL-4, that are antagonist to those secreted by TH1 cells. The antagonism between cytokines is an important point of balance for the immune system and the NEI interactions.
Cortisol also has a high density of brain receptors located mainly in the hippocampus. Under normal conditions, when the stressful stimulus disappears, proinflammatory cytokine production decreases and cortisol leads the NEI interactions to the basal condition again.
The long-term presence of stressful stimuli causes the chronic increase of circulating cortisol, resulting in an impairment of the NEI interactions, which can originate infectious, chronic or autoimmune diseases, as well as psychiatric disorders like depression, schizophrenia, Alzheimer’s disease and anorexia.
Every one of us faces a series of systemic and psychological stressful stimuli all through our lives. The intensity and duration of those stimuli will depend on our capacity to cope with them; this capacity is sustained by our genetic background and the learning provided by our social and environmental experiences.
During these last years, the study of the NEI interactions has acquired great interest because the knowledge generated within this area will allow the development of new and efficient therapeutical approaches to improve and control several physical and psychiatric disorders.


REFERENCES

  1. ABEL T, NGUYEN PV, BARAD M, DEUEL TA, KANDEL ER, BOURTCHOULADZE R: Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampusbased long-term memory. Cell, 88(5):615-26, 1997.

  2. ARAQUE A, CARMIGNOTO G, HAYDON PG: Dynamic signaling between astrocytes and neurons. Annu Rev Physiol, 63:795-813, 2001.

  3. ARIMURA A: Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems. Jpn J Physiol, 48(5):301-331, 1998.

  4. BENNET MR: The concept of long- term potentiation of transmission at synapse. Prog Neurobiol, 60:109- 137, 2000.

  5. BLISS TVP, COLLINGRIDGE GL: A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 361:31- 39, 1993.

  6. CALIXTO E, THIELS E, KLANN E, BARRIONUEVO N: Early Maintenance of Hippocampal Mossy fiber- long-term potentiation depends on protein and RNA synthesis and presynaptic granule cell integrity. J Neurosci, 23(12):4842-49, 2003.

  7. CAVUS I, TEYLER T. Two forms of long- term potentiation in area CA1 activate different signal transduction cascades. J Neurophysiol, 76:3038- 047, 1996.

  8. CHAPMAN PF, BELLAVANCE LL: Induction of long-term potentiation in the basolateral amygdala does not depend on NMDA receptor activation. Synapse, 11:310-318, 1992.

  9. CHAPMAN PF, RAMSAY MF, KREZEL W, KNEVETT SG: Synaptic Plasticity in the Amygdala. Comparisons with Hippocampus. Ann NY Acad Sci, 985:114-124, 2003.

  10. CHRISTOPHONE J: Type I receptors for PACAP (a neuropeptide even more important than VIP?). Biochim Biophys Acta, 1154(2):183-199, 1993.

  11. COLLINGRIDGE GL, KEIIL SJ, MCLENNAN H: Excitatory amino acids in synaptic transmission in the Schaffer collateral commissural pathway of the rat hippocampus. J Physiol (Lond.), 334:33-46, 1983.

  12. DUAN S, ANDERSON CH, KEUNG E, CHEN Y, CHEN YI, SWANSON R: P2X7 Receptor. Mediated release of excitatory amino acids from astrocytes. J Neurosci, 234):1320- 28, 2003.

  13. FORREST D, YUZAKI M, SOARES HD, NG L, LUK DC, SHENG M, STEWART CL, MORGAN JI, CONNOR JA, CURRAN T. Targeted disruption of NMDA receptor-1 gene abolishes NMDA response and results in neonatal death. Neuron, 13(2):325-38, 1994.

  14. FREY U, KRUG M, REYMANN KG, MATTHIES H:Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res, 452(1-2):57-65, 1988.

  15. FREY U, HUANG YY, KANDEL ER: Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science, 260(5114):1661-64, 1993.

  16. FREY U, MORRIS RG: Synaptic tagging and long term potentiation. Nature, 385:533-536, 1997.

  17. FREY U, KRUG M, BRODEMANN R, REYMANN K, MATTHIES H: Long- term potentiation induced in dendrites separated from rat´s CA1 pyrmidal somata does not establish a late phase. Neuroscience Lett, 97:135-139, 1989.

  18. GEBREMEDHIN D, YAMAURA K, ZHANG CH, BYLUND J, KOEHLER R, HARDNER D: Metabotropic glutamate receptor activation enhaces the activities of two types of Ca2+ - activated K+ channels in rat hippocampal astrocytes. J Neurosci, 23(5):1678-87, 2003.

  19. GERLAI R: Learning from files. Trends Neurosciences, 24(9):502, 2001.

  20. GERLAI R, WOJTOWICZ JM, MARKS A, RODER J: Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice. Learn Mem, 2(1):26-39, 1995.

  21. GIESE KP, FEDEROV NB, FILIPKOWSKI RK: Autophosphorylation at threonine 286 of the calciumcalmodulin- kinase II in LTP and learning. Science, 279:870, 1998.

  22. GOOSENS KA, HOLT W, MAREN S: A role for amygdaloid PKA and PKC in the acquisition of long-term conditional fear memories in rats. Behav Brain Res, 114(1-2):145-152, 2000.

  23. GROVER LM, TEYLER TJ: Two components of long-term potentiation induced by different patterns of afferent activation. Nature, 347:477-479, 1990.

  24. GROVER LM, TEYLER TJ: Different mechanisms may be required for maintenance of NMDA receptor-dependent and independent forms of long-term potentiation. Synapse, 19(2):121-33, 1995.

  25. HARRIS EW, COTMAN CW: Long- term potentiation of guinea pig mossy fiber responses is not blocked by N- methyl- D- aspartate antagonists. Neurosci Lett, 70:132- 137, 1986.

  26. HARRIS EW, GANONG AH, COTMAN CW: Long-term potentiation in the hippocampus involves activation of Nmethyl- D- aspartate receptors. Brain Res, 323:132-137, 1984.

  27. HARRIS KM: How multiple-synapse boutons could preserve input specificity during an interneuronal spread of LTP. Trends in Neurosci, 18:365-369, 1995.

  28. HASHIMOTO H, NOGI H, MORI K, OHISHI H, SHIGEMOTO R, YAMAMOTO K, MATSUDA T, MIZUNO N, NAGAT S, BABA A: Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: an in situ hybridization study. J Comp Neurol, 371(4):567-577, 1996.

  29. HU JY, MENG X, SCHACHER S: Redistribution of syntaxin mRNA in neuronal cell bodies regulates protein expression and transport during synapse formation and long-term synaptic plasticity. J Neurosci, 23:1804-15, 2003.

  30. HUANG YY, KANDEL ER: Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron, 21(1):169-178, 1998.

  31. HUANG YY, LI X, KANDEL ER: cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase. Cell, 79(1):69-79, 1994.

  32. HUANG YY, KANDEL ER: Postsynaptic induction and PKA- dependent expression of LTP in the lateral amygdala. Neuron, 21:169-178, 1998.

  33. IMPEY S, SMITH DM, OBRIETAN K, DONAHUE R, WADE C, STORM DR: Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci, 1:595-601, 1998.

  34. JOB C, EBERWINE J: Localization and translation of mRNA in dendrites and axons. Nature Reviews, 2:889-898, 2001.

  35. JOSSELYN SA, SHI C, CARLEZON WA Jr, NEVE RL, NESTLER EJ, DAVIS M: Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala. J Neurosci, 21(7):2404-12, 2001.

  36. KACHARMINA JE, JOB C, CRINO P, EBERWINE J: Stimulation of glutamate receptor protein synthesis and membrane insertion within isolated neural dendrites. Proc Natl Acad Sci USA, 97:11545-50, 2001.

  37. KATO K, KUROBE N, SUZUKI F, MORISHITA R, ASANO T, SATO T, INAGAKI T: Concentrations of several proteins characteristic of nervous tissue in cerebral cortex of patients with Alzheimer’s disease. J Mol Neurosci, 3(2):95-99, 1991.

  38. KENNEDY MB, GREENGARD P: Two calcium/ calmodulin-dependent protein kinases, which are highly concentrated in brain, phosphorylate protein I at distinct sites. Proc Natl Acad Sci USA, 78:1293-97, 1981.

  39. KIM CH, LISMAN JE: A role of actin filament in synaptictransmission and long-term potentiation. J Neurosci, 19: 4314- 24, 1999.

  40. KRUCKER T, SIGGINS GR, HALPAIN S: Dynamic actin filaments are required for stable long- term potentiation (LTP) in area CA1 of the hippocampus. Proc Natl Acad Sci USA, 97:6856-61, 2000.

  41. KRUG M, LÖSSNER B, OU T: Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats. Brain Res Bull, 13:39-42, 1984.

  42. LEFF P, ROMO H, MATUS M, HERNANDEZ A, CALVA JC, ACEVEDO R, TORNER C, GUTIERREZ R, ANTON B: Understanding the neurobiological mechanism of learning and memory: Memory systems of the brain, long-term potentiation and synaptic plasticity. Part IIIB. Salud Mental, 25(4):78-94, 2002.

  43. LIN CH, YEH SH, LEU TH, CHANG WC, WANG SH, GEAN PW: Identification of calcineurin as a key signal in the extinction of fear memory. J Neurosci, 23(5):1574-79, 2003.

  44. LIN CH, YEH SH, LIN CH, LU KT, LEU TH, CHANG WC, GEAN PW: A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala. Neuron, 31(5):841-851, 2001.

  45. LISMAN J, MALENKA RC, NICOLL RA: Learning mechanisms: the case for CaMKII. Science, 276:2001-2002, 1997.

  46. LOPEZ-GARCIA JC: Two diferent forms of long-term potentiation in the hippocampus. Neurobiology, 6:75-98, 1998.

  47. LU KT, WALKER DL, DAVIS M: Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle. J Neurosci, 21(16):RC162, 2001.

  48. LYNCH G, LARSON S, KELSO S et al.: Intracellular injections of EGTA block the induction of hippocampal long- term potentiation. Nature, 305:719-721, 1983.

  49. MALINOW R, MALENKA RC: AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci, 25:103-126, 2002.

  50. MAREN S: Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci, 24:897-931, 2001.

  51. MAREN S: Long-term potentiation in the amygdala: a mechanism for emotional learning and memory. Trends Neurosci, 22(12):561-567, 1999.

  52. MATTHIAS K, KIRCHHOFF F, SEIFERT G, HÜTTMANN, MATYASH M, KETTENMANN H, STEINHÄUSER Ch: Segregated expression of AMPA- type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. J Neurosci, 23(5):1750, 2003.

  53. McCALL MA, GREGG RG, BEHRINGER RR, BRENNER M, DELANEY CL, GALBREATH EJ, ZHANG CL, PEARCE RA, CHIU SY, MESSING A: Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proc Natl Acad Sci USA, 93(13):6361-6, 1996.

  54. McGAUGH JL: Memory consolidation and the amygdala: a systems perspective. Trends Neurosci, 25(9):456-461, 2002.

  55. NADER K, SCHAFE GE, LEDOUX JE: Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature, 406(6797): 722-726, 2000.

  56. NAYAK A, ZASTROW DJ, LICKTEIG R, ZAHNISER NR, BROWNING MD: Maintenance of late-phase LTP is accompanied by PKA-dependent increase in AMPA receptor synthesis. Nature, 394(6694):680-683, 1998.

  57. NGUYEN PV, ABEL T, KANDEL ER, BOURTCHOULADZE R: Strain-dependent differences in LTP and hippocampus-dependent memory in inbred mice. Learn Mem,7(3):170-9, 2000.

  58. NGUYEN PV, ABEL T, KANDEL E: Requirement of a critical period of transcription for induction of a late phase of LTP. Science, 265:1104-07, 1994.

  59. NGUYEN PV, KANDEL ER: A macromolecular synthesisdependent late phase of long-term potentiation requiring cAMP in the medial perforant pathway of rat hippocampal slices. J Neurosci, 16(10):3189-98, 1996.

  60. NICOLL RA, MALENKA RC: Contrasting properties of two forms of long- term potentiation in the hippocampus. Nature 377:115-118, 1995.

  61. NISHIYAMA H, KNÖPFEL T, ENDO S, ITOHARA S: Glial protein S100B modulates long-term neuronal synaptic plasticity. Proc Natl Acad Sci USA, 99(6):4037-42, 2002.

  62. OTANI S, ABRAHAM WC: Inhibition of protein synthesis in the dentate gyrus, but not the entorhinal cortex, blocks maintenance of long-term potentiation in rats. Neurosci Lett, 106(1-2):175-80, 1989.

  63. OTTO C, KOVALCHUK Y, WOLFER DP, GASS P, MARTIN M et al.: Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type-I receptor-deficient mice. J Neurosci, 21(15):5520-27, 2003.

  64. OTTO C, ZUCHRATTER W, GASS P, AND SCHÜTZ G: (Presynaptic localization of the PACAP-typeI-receptor in hippocampal and cerebellar mossy fibers. Brain Res Mol Brain Res, 66(1-2):163-174, 1999.

  65. PAREKH A: Neuronal Ca2+ signaling: pathways and targets. Trends Neurosci, 24(7):369-370, 2001.

  66. PARPURA V, HAYDON PG: Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons. Proc Natl Acad Sci USA, 97(15):8629-34, 2000.

  67. POPOV N, SCHULZECK S, PANKOVA TM, RATUNYAK AS et al.: Alterations in calmodulin and S-100 protein content of hippocampal slices during long-term potentiation. Biomed Biochim Acta, 47(2):189-195, 1988.

  68. RAMMES G, STECKLER T, KRESSE A, SCHUTZ G, ZIEGLGANSBERGER W, LUTZ B: Synaptic plasticity in the basolateral amygdala in transgenic mice expressing dominant-negative cAMP response element-binding protein (CREB) in forebrain. Eur J Neurosci, 12(7):2534-46, 2000.

  69. RAMSAY MF, PAKHOTIN P, CHAPMAN PF et al.: Different LTP induction mechanisms in somatosensory cortex and basolateral amygdala. Soc Neuro Abstr, 21:275.1, 2001.

  70. REEVES RH, YAO J, CROWLEY MR, BUCK S, ZHANG X et al.: Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice. Proc Natl Acad Sci USA, 91:5359-63, 1994.

  71. SASAKI N, TOKI S, CHOWEI H, SAITO T, NAKANO N, et al.: Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease. Brain Res, 888(2):256-262, 2001.

  72. SCHAFE GE, LeDOUX JE: Memory consolidation of auditory pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala. J Neurosci, 20(18):RC96, 2000.

  73. SHIBUKI K, GOMI H, CHEN L, BAO S, KIM JJ et al.: Deficient cerebellar long-term depression, impaired eyeblink conditioning, and normal motor coordination in GFAP mutant mice. Neuron, 16(3):587-99, 1996.

  74. SHIVERS BD, GORCS TJ, GOTTSCHALL PE, ARIMURA A: Two high affinity-binding sites for pituitary adenylate cyclase-activating polypeptide have different tissue distributions. Endocrinology. 128(6):3055-3065, 1991.

  75. SILVA AJ, STEVENS CF, TONEGAWA S, WANG Y: Deficient hippocampal long-term potentiation in alphacalcium-calmodulin kinase II mutant mice. Science, 257:201-206, 1992.

  76. SMITH WB, AAKALU G, SCHUMAN EM: Local protein synthesis in neurons. Curr Biol, 11:R901-R903, 2001.

  77. SPIER AD: Dendritic receptors made to order. Trends Neurosci, 24(2):76, 2001.

  78. STEWARD O, WORLEY PF: Local synthesis of proteins at synaptic sites on dendrites: role in synaptic plasticity and memory consolidation? Neurobiol. Learn Mem, 78:508- 527, 2002.

  79. TSIEN JZ, HUERTA PT, TONEGAWA S: The essential role of hippocampal CA1 NMDA receptor dependent synaptic. Cell, 87:1327-38, 1996.

  80. WEISSKOPF MG, NICOLL RA: Presynaptic changes during mossy fiber LTP revealed by NMDA receptor-mediated synaptic response. Nature, 376:256-259, 1995.

  81. WEISSKOPF MG, LEDOUX JE: Distinct populations of NMDA receptors at subcortical and cortical inputs to principal cells of the lateral amygdala. J Neurophysiol, 81:930-934, 1999.

  82. WEISSKOPF MG, NICOLL RA: Presynaptic changes during mossy fiber LTP revealed by NMDA receptor-mediated synaptic responses. Nature, 376:256-259, 1995.

  83. WHITAKER-AZMITIA PM, WINGATE M, BORELLA A, GERLAI R, RODER J, AZMITIA EC: Transgenic mice overexpressing the neurotrophic factor S-100 beta show neuronal cytoskeletal and behavioral signs of altered aging processes: implications for Alzheimer’s disease and Down’s syndrome. Brain Res, 776(1-2):51-60, 1997.

  84. XIANG Z, GREENWOOD AC, KAIRISS EW, BROWN TH: Quantal mechanism of long-term potentiation in hippocampal mossy- fiber synapses. J Neurophysiol, 71:2552-56, 1994.

  85. YAMAGATA K, ANDREASSON KI, SUDIURA H, MARUE, DOMINIQUE M et al.: Arcadlin is a neural activityregulated cadherin involved in long-term potentiation. J Biol Chem, 274: 19473-79, 1999.

  86. YECKEL MF, KAPUR A, JOHNSTON D: Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism. Nat Neurosci, 2:625-633, 1999.

  87. ZIMMER DB, CORNWALL EH, LANDAR A, SONG W: The S100 protein family: history, function, and expression. Brain Res Bull, 37(4):417-29, 1995.




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