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An Overview of Brain-Derived Neurotrophic Factor and Implications for Excitotoxic Vulnerability in the Hippocampus

By Patrick S. Murray and Philip V. Holmes

Abstract

The present paper examines the nature and function of brain-derived neurotrophic factor (BDNF) in the hippocampal formation and the consequences of changes in its expression. The paper focuses on literature describing the role of BDNF in hippocampal development and neuroplasticity. BDNF expression is highly sensitive to developmental and environmental factors, and increased BDNF signaling enhances neurogenesis, neurite sprouting, electrophysiological activity, and other processes reflective of a general enhancement of hippocampal function. Such increases in activity may mediate beneficial effects such as enhanced learning and memory. However, the increased activity also comes at a cost: BDNF plasticity renders the hippocampus more vulnerable to hyperexcitability and/or excitotoxic damage. Exercise dramatically increases hippocampal BDNF levels and produces behavioral effects consistent with this phenomenon. In analyzing the literature regarding exercise-induced regulation of BDNF, this paper provides a theoretical model for how the potentially deleterious consequences of BDNF plasticity may be modulated by other endogenous factors. The peptide galanin may play such a role by regulating hippocampal excitability

Topics: Review Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3182334
Provided by: PubMed Central

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Citations

  1. (1997). A lipidanchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway,”
  2. (2003). a m s d e n ,N .C .B e r c h t o l d ,J .P a t r i c kK e s s l a k
  3. (1999). a n dE .A .C a v a l h e i r o ,“ E ffect of physical exercise on seizure occurrence in a model of temporal lobe epilepsy in rats,”
  4. (2007). a r k ,a n dH .J .C h o , “Expression of brain-derived neurotrophic factor in the rat forebrain and upper brain stem during postnatal development: an immunohistochemical study,”
  5. (2000). A.Bacon etal., “Modulation of hippocampal excitability and seizures by galanin,”
  6. (1999). Actions of brain-derived neurotrophic factor in slices from rats with spontaneous seizures and mossy fiber sprouting in the dentate gyrus,”
  7. (2002). Activation of Rac GTPase by p75 is necessary for c-jun N-terminal kinasemediated apoptosis,”
  8. (2000). Activity-dependent release of endogenousbrain-derivedneurotrophicfactorfromprimary sensory neurons detected by ELISA in situ,”
  9. (1999). Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor,”
  10. (1992). Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases,”
  11. (2005). Backpropagating action potentials in neurones: measurement, mechanisms and potential functions,”
  12. (2008). BackpropagatingactionpotentialstriggerdendriticreleaseofBDNFduring spontaneous network activity,”
  13. (2005). BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis,”
  14. (1991). BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from
  15. (2009). BDNF signaling in the formation, maturation and plasticity of glutamatergic and GABAergic synapses,”
  16. (1999). Biochemical and functional interactions between the neurotrophin receptors trk and p75(NTR),”
  17. (2008). Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition,”
  18. (2004). Brain-derived neurotrophic factor,”
  19. (2004). Brain-derived neurotrophic factorinduceshyperexcitablereentrantcircuitsinthedentate gyrus,”
  20. (2007). C a l d e i r a ,C .V .M e l o ,D .B .P e r e i r a ,R .F .C a rv a l h o
  21. (2010). C he n,J .C.Laut e rborn,D
  22. (2011). C.Heinrich,S.L¨ ahteinen,F.Suzukietal.,“IncreaseinBDNFmediated TrkB signaling promotes epileptogenesis in a mousemodelofmesialtemporallobeepilepsy,”
  23. (2007). Ca2+ signaling in dendritic spines,”
  24. (2003). Can the brain be protected through exercise? Lessons from an animal model of parkinsonism,”
  25. (1999). Cell survival promoted by the RasMAPK signaling pathway by transcription-dependent and -independent mechanisms,”
  26. (2010). Changes in spatial memory and BDNF expression to concurrent dietary restriction and voluntary exercise,”
  27. (2009). Chronic activity wheel running reduces the severity of kainic acid-induced seizures in the rat: possible role of galanin,”
  28. (2000). Circulating insulin-like growth factor I mediates effects of exercise on the brain,”
  29. (1995). Coexisting neurotransmitters in central noradrenergic neurons,” in Psychopharmacology: The Fourth Generation of Progress,F .B l o o ma n dD
  30. (2002). D a n z e r ,K .R .C .C r o o k s ,D .C .L o ,a n dJ .O .M c N a m a r a , “Increased expression of brain-derived neurotrophic factor induces formation of basal dendrites and axonal branching in dentate granule cells in hippocampal explant cultures,”
  31. (1999). Depolarization and neurotrophins converge on the phosphatidylinositol 3- kinase-Akt pathway to synergistically regulate neuronal survival,”
  32. (2004). Development of the telencephalon: neural stem cells, neurogenesis and neuronal migration,”
  33. (2000). Differential effects of BDNF, ADNF9, and TNF on levels of NMDA receptor subunits, calcium homeostasis, and neuronal vulnerability to excitotoxicity,”
  34. (1995). Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins,”
  35. (1997). Distribution of brain-derived neurotrophic factor in rats and its changes with development in the brain,”
  36. (1998). e r n y h o u g h ,L .T .D i e m e l ,a n dD .R .T o m l i n s o n ,“ T a r g e t tissue production and axonal transport of neurotrophin-3 are reduced in streptozocin-diabetic rats,”
  37. (1994). E.J.Williams,F.S.Walsh,andP.Doherty,“Theproductionof arachidonic acid can account for calcium channel activation in the second messenger pathway underlying neurite outgrowth stimulated by NCAM, N-cadherin, and L1,”
  38. (2003). Effects of chronic exercise and imipramine on mRNA for BDNF after olfactory bulbectomy in rat,”
  39. (2004). Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male sprague—dawley rats in vivo,”
  40. (2004). Effects of β-adrenoreceptor blockade during chronic exercise on contextual fear conditioning and mRNA for galanin and brain-derived neurotrophic factor,”
  41. (2005). Electrophysiological studies on galanin effects in brain - Progress during the last six years,”
  42. (2003). Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways,”
  43. (1993). Excitotoxicity and selective neuronal loss in epilepsy,”
  44. (2005). Exercise activates the phosphatidylinositol 3-kinase pathway,”
  45. (2010). Exercise and time-dependent benefits to learning and memory,”
  46. (2006). Exercise differentially regulates synaptic proteins associated tothefunctionofBDNF,”BrainResearch,vol.1070,no.1,pp. 124–130,
  47. (2009). Exercise increases BDNF levels in the striatum and decreases depressive-like behavior in chronically stressed rats,”
  48. (2004). Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor,”
  49. (2005). Exercise, but not environmental enrichment, improves learning after kainic acid-induced hippocampal neurodegeneration in association with an increase in brain-derived neurotrophic factor,”
  50. (2004). Exerciseinduced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia,”
  51. (2004). Galanin acts as a neuroprotective factor to the hippocampus,”
  52. (1986). Galaninlike immunoreactivity in hippocampal afferents in the rat, with special reference to cholinergic and noradrenergic inputs,”
  53. (1986). Glutamate and anoxic neuronal death in vitro,”
  54. (1995). Glutamate-induced neuronal death: a succession of necrosis or12
  55. (1995). Glutamate, calcium, and free radicals as mediators of ischemic brain damage,”
  56. (1997). Grb2-associated binder1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor,”
  57. (1995). Hippocampal long-term potentiation is impairedinmicelackingbrain-derivedneurotrophicfactor,”
  58. (2006). Hippocampal long-termpotentiationissupportedbypresynapticandpostsynaptic tyrosine receptor kinase B-mediated phospholipase Cγ signaling,”
  59. (1998). Ib´ a˜ nez, “Neurotrophin-7: a novel member of the neurotrophin family from the zebrafish,”
  60. (1999). Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice,”
  61. (2005). Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats,”
  62. (2001). Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus,”
  63. (1997). Insulin receptor substrate (IRS)-1 and IRS-2 are tyrosine- phosphorylated and associated with phosphatidylinositol 3-kinase in response to brain-derived neurotrophic factor in cultured cerebral cortical neurons,”
  64. (2003). Interplay between brain-derived neurotrophic factor and signal transductionmodulatorsintheregulationoftheeffectsofexercise on synaptic-plasticity,”
  65. (1987). Ionic dependence of glutamate neurotoxicity,”
  66. (2010). Locus coeruleus galanin expression is enhanced after exercise in rats selectively bred for high capacity for aerobic activity,” Peptides,
  67. (1994). Mice lacking brainderived neurotrophic factor develop with sensory deficits,”
  68. N-methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurologicaldisease,”Neuroscientist,vol.11,no.1,pp.37–49,2005.
  69. (1999). Neuronal life and death decisions:functional antagonism between theTrkand p75neurotrophin receptors,”
  70. (2004). Neuroprotection against transient cerebral ischemia by exercise pre-conditioning in rats,”
  71. (1994). Neurotrophic factors: from molecule to man,”
  72. (2002). Neurotrophin signaling through the p75 neurotrophin receptor,”
  73. (1994). Neurotrophin-6 is a new member of the nerve growth factor family,”
  74. (2001). Neurotrophins and neuronal differentiation in the central nervous system,”
  75. (1999). Neurotrophins and synaptic plasticity,”
  76. (2001). Neurotrophins: roles in neuronal development and function,”
  77. (1990). NT3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression,”
  78. (2005). ochl, “Low concentrations of aggregated β-amyloid induce neurite formation via the neurotrophin receptor p75,”
  79. (1998). Oliff,N .C .B e r c h t o l d ,P .I s a c k s o n ,a n dC .W .C o t m a n , “Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus,”
  80. (2005). P.A.Adlard,V.M.Perreau,andC.W.Cotman,“Theexerciseinduced expression of BDNF within the hippocampus varies across life-span,” Neurobiology of Aging,v o l .2 6 ,n o .4 ,p p .
  81. (1999). p75(NTR) immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles,”
  82. (2001). Physical activity and risk of cognitive impairmentanddementiainelderlypersons,”ArchivesofNeurology,
  83. (2001). Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mitogen-activated protein kinase in the rat hippocampus,”
  84. (2004). Physical training reverts hippocampal electrophysiological changes in rats submitted to the pilocarpine model of epilepsy,”
  85. (2001). Prepro-galanin messenger RNA levels are increased in rat locus coeruleus after treadmill exercise training,”
  86. (2006). Presynaptic plasticity in an immature neocortical network requires NMDA receptor activation and BDNF release,”
  87. (1999). Protein kinase Cδ mediates neurogenic but not mitogenic activation of mitogen-activated protein kinase in neuronal cells,”
  88. (1990). R.Klein,D.Conway,L.F.Parada,andM.Barbacid,“ThetrkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain,”
  89. (1996). Regulated release and polarized localization of brain-derived neurotrophic factor in hippocampal neurons,”
  90. (1991). Regulation by synapsin I and Ca2(+)-calmodulin-dependent protein kinase II of transmitter releaseinsquidgiantsynapse,”J o urnalo fPh ysio logy,vol.436,
  91. (2005). Regulation of limbic status epilepticus by hippocampal galanin type 1 and type 2 receptors,”
  92. (1997). Regulation of phosphoinositide-specific phospholipase C isozymes,”
  93. (2000). Regulation of retinal neurite growth by alterations
  94. (1999). Running enhances neurogenesis, learning, and long-term potentiation in mice,”
  95. (2009). Running exerciseinduced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent,”
  96. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus,” Nature Neuroscience,v o l .2 ,n o .3 ,p p .
  97. (2004). Russell,“Voluntaryrunningprovides neuroprotectioninrats after 6-hydroxydopamine injection into the medial forebrain bundle,”
  98. S c h w a r t z ,P .R .B o r g h e s a n i
  99. (2004). S.Vaynman,Z.Ying,andF.G´ omez-Pinilla,“ExerciseInduces BDNF and Synapsin I to Specific Hippocampal Subfields,”10
  100. (1992). Shc proteins are phosphorylated and regulated by the vSrc and v-Fps protein-tyrosine kinases,”
  101. (2003). Short-term frequencydependent plasticity at recurrent mossy fiber synapses of the epileptic brain,”
  102. (1997). Signal transduction by the neurotrophinreceptors,”CurrentOpinioninCellBiology,vol.
  103. (1998). Soomets et al., “Galanin modulation of seizures and seizure modulation of hippocampal galanin in animal models of status epilepticus,”
  104. (2001). Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses,”
  105. (2000). Synaptophysin regulates clathrin-independent endocytosis of synaptic vesicles,”
  106. (1994). Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development,”
  107. (1984). The development of the rat spinal cord,”
  108. (2005). The effect of exercise on hippocampal integrity: review of recent research,”
  109. (1994). The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development,”
  110. (1998). The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death,”
  111. (2000). The role of brainderived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving trkB,”
  112. (1999). The role of excitotoxicity in neurodegenerative disease: implications for therapy,”
  113. (2001). The uniqueness of being a neurotrophin receptor,”
  114. (2010). Treadmill exercise prevents aging-induced failure of memory through an increase in neurogenesis and suppression of apoptosis in rat hippocampus,”
  115. (2001). Trk receptors: mediators of neurotrophin action,”
  116. (1991). trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor,”
  117. (1991). Tyrosine phosphorylationandtyrosinekinaseactivityofthetrkprotooncogene product induced by
  118. (1996). Virus-mediated gene transfer into hippocampal CA1 region restores longterm potentiation in brain-derived neurotrophic factor mutantmice,”ProceedingsoftheNationalAcademyofSciences of the United
  119. (2009). Voluntary exercise and caloric restriction enhance hippocampal dendritic spine densityandBDNFlevelsindiabeticmice,”Hippocampus,vol.
  120. (2006). Voluntary exercise and clomipramine treatment elevate prepro-galanin mRNA levels in the locus coeruleus in rats,”