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Alterations in discrete glutamate receptor subunits in adult mouse dentate gyrus granule cells following perforant path transection

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Abstract

Custom-designed microarray analysis was utilized to evaluate expression levels of glutamate receptors (GluRs) and GluR-interacting protein genes within isolated dentate gyrus granule cells following axotomy of the principal input, the perforant path (PP). Dentate gyrus granule cells were evaluated by microdissection via laser capture microdissection, terminal continuation RNA amplification, and microarray analysis following unilateral PP transections at seven time points. Expression profiles garnered from granule cells on the side ipsilateral to PP transections were compared and contrasted with naive subjects and mice subjected to unilateral occipital cortex lesions. Selected microarray observations were validated by real-time quantitative PCR analysis. Postlesion time-dependent alterations in specific α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, kainate receptors, N-methyl-d-aspartate (NMDA) receptors, and GluR-interacting protein genes were found across the time course of the study, suggesting a neuroplasticity response associated with the transsynaptic granule cell alterations following axotomy of incoming PP terminals.

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References

  1. Aldskogius H, Arvidsson J, Grant G (1985) The reaction of primary sensory neurons to peripheral nerve injury with particular emphasis on transganglionic changes. Brain Res 357:27–46

    CAS  Google Scholar 

  2. Santos AF, Caroni P (2003) Assembly, plasticity and selective vulnerability to disease of mouse neuromuscular junctions. J Neurocytol 32:849–862

    Article  CAS  Google Scholar 

  3. Squire LR, Stark CE, Clark RE (2004) The medial temporal lobe. Annu Rev Neurosci 27:279–306

    Article  CAS  Google Scholar 

  4. Steward O, Scoville SA (1976) Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat. J Comp Neurol 169:347–370

    Article  CAS  Google Scholar 

  5. Steward O, Vinsant SL (1983) The process of reinnervation in the dentate gyrus of adult rats: a quantitative electron microscopic analysis of terminal proliferation and reactive synaptogenesis. J Comp Neurol 214:370–386

    Article  Google Scholar 

  6. Gazzaley AH, Benson DL, Huntley GW, Morrison JH (1997) Differential subcellular regulation of NMDAR1 protein and mRNA in dendrites of dentate gyrus granule cells after perforant path transection. J Neurosci 17:2006–2017

    CAS  Google Scholar 

  7. Ginsberg SD (2005) Glutamatergic neurotransmission expression profiling in the mouse hippocampus after perforant-path transection. Am J Geriatr Psychiatry 13:1052–1061

    Google Scholar 

  8. Hardman R, Evans DJ, Fellows L, Hayes B, Rupniak HT, Barnes JC, Higgins GA (1997) Evidence for recovery of spatial learning following entorhinal cortex lesions in mice. Brain Res 758:187–200

    Article  CAS  Google Scholar 

  9. Steward O, Loesche J, Horton WC (1977) Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: open field activity and cue utilization following bilateral entorhinal cortex lesions. Brain Res Bull 2:41–48

    Article  CAS  Google Scholar 

  10. Reeves TM, Smith DC (1987) Reinnervation of the dentate gyrus and recovery of alternation behavior following entorhinal cortex lesions. Behav Neurosci 101:179–186

    Article  CAS  Google Scholar 

  11. Matthews DA, Cotman C, Lynch G (1976) An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration. Brain Res 115:1–21

    Article  CAS  Google Scholar 

  12. Matthews DA, Cotman C, Lynch G (1976) An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. II. Reappearance of morphologically normal synaptic contacts. Brain Res 115:23–41

    Article  CAS  Google Scholar 

  13. Deller T, Nitsch R, Frotscher M (1995) Phaseolus vulgaris-leucoagglutinin tracing of commissural fibers to the rat dentate gyrus: evidence for a previously unknown commissural projection to the outer molecular layer. J Comp Neurol 352:55–68

    Article  CAS  Google Scholar 

  14. Nadler JV, Cotman CW, Lynch G (1977) Histochemical evidence of altered development of cholinergic fibers in the rat dentate gyrus following lesions. I. Time course after complete unilateral entorhinal lesion at various ages. J Comp Neurol 171:561–587

    Article  CAS  Google Scholar 

  15. Marrone DF, Petit TL (2002) The role of synaptic morphology in neural plasticity: structural interactions underlying synaptic power. Brain Res Brain Res Rev 38:291–308

    Article  Google Scholar 

  16. Martin LJ, Blackstone CD, Levey AI, Huganir RL, Price DL (1993) Cellular localizations of AMPA glutamate receptors within the basal forebrain magnocellular complex of rat and monkey. J Neurosci 13:2249–2263

    CAS  Google Scholar 

  17. Martin LJ, Blackstone CD, Huganir RL, Price DL (1992) Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron 9:259–270

    Article  CAS  Google Scholar 

  18. Petralia RS, Wenthold RJ (1992) Light and electron immunocytochemical localization of AMPA-selective glutamate receptors in the rat brain. J Comp Neurol 318:329–354

    Article  CAS  Google Scholar 

  19. Petralia RS, Yokotani N, Wenthold RJ (1994) Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody. J Neurosci 14:667–696

    CAS  Google Scholar 

  20. Petralia RS, Wang Y-X, Wenthold RJ (1994) Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies. J Comp Neurol 349:85–110

    Article  CAS  Google Scholar 

  21. Rothstein JD, Martin LJ, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (1994) Localization of neuronal and glial glutamate transporters. Neuron 13:713–725

    Article  CAS  Google Scholar 

  22. Hein C, Horvath E, Kugler P (2001) Glutamate transporter expression in astrocytes of the rat dentate gyrus following lesion of the entorhinal cortex. Eur J Neurosci 13:1839–1848

    Article  CAS  Google Scholar 

  23. Dong H, Zhang P, Song I, Petralia RS, Liao D, Huganir RL (1999) Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2. J Neurosci 19:6930–6941

    CAS  Google Scholar 

  24. Hirbec H, Francis JC, Lauri SE, Braithwaite SP, Coussen F, Mulle C, Dev KK, Coutinho V, Meyer G, Isaac JT, Collingridge GL, Henley JM (2003) Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP. Neuron 37:625–638

    Article  CAS  Google Scholar 

  25. Rosenzweig ES, Barnes CA (2003) Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Prog Neurobiol 69:143–179

    Article  CAS  Google Scholar 

  26. Nakao K, Ikegaya Y, Yamada MK, Nishiyama N, Matsuki N (2003) Fimbrial control of bidirectional synaptic plasticity of medial perforant path-dentate transmission. Synapse 47:163–168

    Article  CAS  Google Scholar 

  27. Adams MM, Gazzaley AH, Morrison JH (2001) Attenuated lesion-induced N-methyl-D-aspartate receptor (NMDAR) plasticity in the dentate gyrus of aged rats following perforant path lesions. Exp Neurol 172:244–249

    Article  CAS  Google Scholar 

  28. Iwakiri M, Mizukami K, Ishikawa M, Hidaka S, Asada T (2002) Alterations of NMDAR1 and NMDAR2a/B immunoreactivity in the hippocampus after perforant pathway lesion. Neuropathology 22:154–160

    Article  Google Scholar 

  29. Ying G, Huang C, Jing N, Zhou C (2001) Identification of differentially expressed genes in the denervated rat hippocampus by cDNA arrays. Neurosci Lett 306:121–125

    Article  CAS  Google Scholar 

  30. Jensen MB, Gonzalez B, Castellano B, Zimmer J (1994) Microglial and astroglial reactions to anterograde axonal degeneration: a histochemical and immunocytochemical study of the adult rat fascia dentata after entorhinal perforant path lesions. Exp Brain Res 98:245–260

    Article  CAS  Google Scholar 

  31. Savaskan NE, Nitsch R (2001) Molecules involved in reactive sprouting in the hippocampus. Rev Neurosci 12:195–215

    CAS  Google Scholar 

  32. Alldred MJ, Che S, Ginsberg SD (2008) Terminal continuation (TC) RNA amplification enables expression profiling using minute RNA input obtained from mouse brain. Int J Mol Sci 9:2091–2104

    Article  CAS  Google Scholar 

  33. Alldred MJ, Che S, Ginsberg SD (2009) Terminal continuation (TC) RNA amplification without second strand synthesis. J Neurosci Methods 177:381–385

    Article  CAS  Google Scholar 

  34. Che S, Ginsberg SD (2004) Amplification of transcripts using terminal continuation. Lab Invest 84:131–137

    Article  CAS  Google Scholar 

  35. Che S, Ginsberg SD (2006) RNA amplification methodologies. In: McNamara PA (ed) Trends in RNA research. Nova Science, Hauppauge, pp 277–301

    Google Scholar 

  36. Ginsberg SD (2005) RNA amplification strategies for small sample populations. Methods 37:229–237

    Article  CAS  Google Scholar 

  37. Ginsberg SD (2008) Transcriptional profiling of small samples in the central nervous system. Meth Mol Biol 439:147–158

    Article  CAS  Google Scholar 

  38. Ginsberg SD, Che S (2002) RNA amplification in brain tissues. Neurochem Res 27:981–992

    Article  CAS  Google Scholar 

  39. Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, 2nd edn. Academic, San Diego

    Google Scholar 

  40. Ginsberg SD, Martin LJ, Rothstein JD (1995) Regional deafferentation down-regulates subtypes of glutamate transporter proteins. J Neurochem 65:2800–2803

    Article  CAS  Google Scholar 

  41. Ginsberg SD, Rothstein JD, Price DL, Martin LJ (1996) Fimbria–fornix transections selectively down-regulate subtypes of glutamate transporter and glutamate receptor proteins in septum and hippocampus. J Neurochem 67:1208–1216

    Article  CAS  Google Scholar 

  42. Ginsberg SD, Che S (2004) Combined histochemical staining, RNA amplification, regional, and single cell analysis within the hippocampus. Lab Invest 84:952–962

    Article  CAS  Google Scholar 

  43. Lee VM-Y, Carden MJ, Schlaepfer WW, Trojanowski JQ (1987) Monoclonal antibodies distinguish several differentially phosphorylated states of the two largest rat neurofilament subunits (NF-H and NF-M) and demonstrate their existence in the normal nervous system of adult rats. J Neurosci 7:3474–3488

    CAS  Google Scholar 

  44. Ginsberg SD, Hemby SE, Lee VM-Y, Eberwine JH, Trojanowski JQ (2000) Expression profile of transcripts in Alzheimer’s disease tangle-bearing CA1 neurons. Ann Neurol 48:77–87

    Article  CAS  Google Scholar 

  45. Ginsberg SD, Hemby SE, Mufson EJ, Martin LJ (2006) Cell and tissue microdissection in combination with genomic and proteomic applications. In: Zaborszky L, Wouterlood FG, Lanciego JL (eds) Neuroanatomical tract tracing 3: molecules, neurons, and systems. Springer, New York, pp 109–141

    Chapter  Google Scholar 

  46. Ginsberg SD, Elarova I, Ruben M, Tan F, Counts SE, Eberwine JH, Trojanowski JQ, Hemby SE, Mufson EJ, Che S (2004) Single cell gene expression analysis: implications for neurodegenerative and neuropsychiatric disorders. Neurochem Res 29:1054–1065

    Google Scholar 

  47. Ginsberg SD, Che S (2005) Expression profile analysis within the human hippocampus: comparison of CA1 and CA3 pyramidal neurons. J Comp Neurol 487:107–118

    Article  CAS  Google Scholar 

  48. Ginsberg SD (2009) Microarray use for the analysis of the CNS. In: Squire LR (ed) Encyclopedia of neuroscience, volume 5. Academic, Oxford, pp 835–841

    Chapter  Google Scholar 

  49. Ginsberg SD, Che S, Counts SE, Mufson EJ (2006) Single cell gene expression profiling in Alzheimer's disease. NeuroRx 3:302–318

    Article  CAS  Google Scholar 

  50. Ginsberg SD, Che S, Wuu J, Counts SE, Mufson EJ (2006) Down regulation of trk but not p75 gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease. J Neurochem 97:475–487

    Article  CAS  Google Scholar 

  51. Kacharmina JE, Crino PB, Eberwine J (1999) Preparation of cDNA from single cells and subcellular regions. Meth Enzymol 303:3–18

    Article  CAS  Google Scholar 

  52. Hemby SE, Trojanowski JQ, Ginsberg SD (2003) Neuron-specific age-related decreases in dopamine receptor subtype mRNAs. J Comp Neurol 456:176–183

    Article  CAS  Google Scholar 

  53. Broberg P (2005) A comparative review of estimates of the proportion unchanged genes and the false discovery rate. BMC Bioinform 6:199

    Article  Google Scholar 

  54. Reiner A, Yekutieli D, Benjamini Y (2003) Identifying differentially expressed genes using false discovery rate controlling procedures. Bioinformatics 19:368–375

    Article  CAS  Google Scholar 

  55. Counts SE, He B, Che S, Ginsberg SD, Mufson EJ (2009) Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer's disease. J Alzheimers Dis 18:885–896

    CAS  Google Scholar 

  56. Kovac AD, Kwidzinski E, Heimrich B, Bittigau P, Deller T, Nitsch R, Bechmann I (2004) Entorhinal cortex lesion in the mouse induces transsynaptic death of perforant path target neurons. Brain Pathol 14:249–257

    Article  Google Scholar 

  57. Nitsch R, Frotscher M (1992) Reduction of posttraumatic transneuronal “early gene” activation and dendritic atrophy by the N-methyl-D-aspartate receptor antagonist MK-801. Proc Natl Acad Sci USA 89:5197–5200

    Article  CAS  Google Scholar 

  58. Bartesaghi R (1994) Hippocampal-entorhinal relationships: electrophysiological analysis of the ventral hippocampal projections to the ventral entorhinal cortex. Neuroscience 61:457–466

    Article  CAS  Google Scholar 

  59. Kelsey JE, Sanderson KL, Frye CA (2000) Perforant path stimulation in rats produces seizures, loss of hippocampal neurons, and a deficit in spatial mapping which are reduced by prior MK-801. Behav Brain Res 107:59–69

    Article  CAS  Google Scholar 

  60. Kienzler F, Norwood BA, Sloviter RS (2009) Hippocampal injury, atrophy, synaptic reorganization, and epileptogenesis after perforant pathway stimulation-induced status epilepticus in the mouse. J Comp Neurol 515:181–196

    Article  Google Scholar 

  61. Takahashi M, Liou S-Y, Kunihara M (1995) Ca2+- and Cl-dependent, NMDA receptor-mediated neuronal death induced by depolarization in rat hippocampal organotypic cultures. Brain Res 675:249–256

    Article  CAS  Google Scholar 

  62. Storm-Mathisen J, Opsahl MW (1978) Aspartate and/or glutamate may be transmitters in hippocampal efferents to septum and hypothalamus. Neurosci Lett 9:65–70

    Article  CAS  Google Scholar 

  63. Schramm M, Eimerl S, Costa E (1990) Serum and depolarizing agents cause acute neurotoxicity in cultured cerebellar granule cells: role of the glutamate receptor responsive to N-methyl-D-aspartate. Proc Natl Acad Sci USA 87:1193–1197

    Article  Google Scholar 

  64. Martin LJ, Al-Abdulla NA, Brambrink AM, Kirsch JR, Sieber FE, Portera-Cailliau C (1998) Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: a perspective on the contributions of apoptosis and necrosis. Brain Res Bull 46:281–309

    Article  CAS  Google Scholar 

  65. Olney JW (2003) Excitotoxicity, apoptosis and neuropsychiatric disorders. Curr Opin Pharmacol 3:101–109

    CAS  Google Scholar 

  66. Sheldon AL, Robinson MB (2007) The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem Int 51:333–355

    Article  CAS  Google Scholar 

  67. Ginsberg SD, Portera-Cailliau C, Martin LJ (1999) Fimbria–fornix transection and excitotoxicity produce similar neurodegeneration in septum. Neuroscience 88:1059–1071

    Article  CAS  Google Scholar 

  68. Ginsberg SD, Martin LJ (2002) Axonal transection in adult rat brain induces transsynaptic apoptosis and persistent atrophy of target neurons. J Neurotrauma 19:99–109

    Article  Google Scholar 

  69. Martin LJ, Sieber FE, Traystman RJ (2000) Apoptosis and necrosis occur in separate neuronal populations in hippocampus and cerebellum after ischemia and are associated with differential alterations in metabotropic glutamate receptor signaling pathways. J Cereb Blood Flow Metab 20:153–167

    Article  CAS  Google Scholar 

  70. Portera-Cailliau C, Price DL, Martin LJ (1997) Non-NMDA and NMDA receptor-mediated excitotoxic neuronal deaths in adult brain are morphologically distinct: further evidence for an apoptosis-necrosis continuum. J Comp Neurol 378:88–104

    Article  CAS  Google Scholar 

  71. Miettinen R, Kotti T, Tuunanen J, Toppinen A, Riekkinen P Sr, Halonen T (1998) Hippocampal damage after injection of kainic acid into the rat entorhinal cortex. Brain Res 813:9–17

    Article  CAS  Google Scholar 

  72. Diekmann S, Ohm TG, Nitsch R (1996) Long-lasting transneuronal changes in rat dentate granule cell dendrites after entorhinal cortex lesion. A combined intracellular injection and electron microscopy study. Brain Pathol 6:205–214

    Article  CAS  Google Scholar 

  73. Nitsch R, Bader S, Frotscher M (1992) Reorganization of input synapses of parvalbumin-containing neurons in the rat fascia dentata following entorhinal lesion. Neurosci Lett 135:33–36

    Article  CAS  Google Scholar 

  74. Nitsch R, Frotscher M (1993) Transneuronal changes in dendrites of GABAergic parvalbumin-containing neurons of the rat fascia dentata following entorhinal lesion. Hippocampus 3:481–490

    Article  CAS  Google Scholar 

  75. Ginsberg SD, Martin LJ (1998) Ultrastructural analysis of the progression of neurodegeneration in the septum following fimbria–fornix transection. Neuroscience 86:1259–1272

    Article  CAS  Google Scholar 

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Acknowledgments

I thank Dr. Shaoli Che, Irina Elarova, John T. Le, and Marc D. Ruben for expert technical assistance. Support for this project comes from the NINDS (NS43939), NIA (AG09466 and AG17617), and the Alzheimer’s Association.

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  1. Departments of Psychiatry, Physiology & Neuroscience, Center for Dementia Research, Nathan Kline Institute, New York University Langone Medical Center, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA

    Stephen D. Ginsberg

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Correspondence to Stephen D. Ginsberg.

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Ginsberg, S.D. Alterations in discrete glutamate receptor subunits in adult mouse dentate gyrus granule cells following perforant path transection. Anal Bioanal Chem 397, 3349–3358 (2010). https://doi.org/10.1007/s00216-010-3826-1

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  • DOI: https://doi.org/10.1007/s00216-010-3826-1

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