Skip to main content

Distinct subcellular localization of BDNF transcripts in cultured hypothalamic neurons and modification by neuronal activation

Journal of Neural Transmission volume 116, pages 23–32 (2009)Cite this article

Abstract

We investigated subcellular localization of total brain-derived neurotrophic factor (BDNF) mRNA (panBDNF) and its different 5′ exon-specific transcripts in cultured hypothalamic neurons. Non-isotopic in situ hybridization (DIG-labeled exon-specific riboprobes) associated with immunocytochemical MAP2 or GFAP labeling was used for detection. We found that under basal conditions panBDNF mRNA was localized in neuronal soma and in primary dendritic processes. Transcripts I and II were weakly expressed in neuronal soma while transcripts IV and VI mRNA were strongly expressed. panBDNF mRNA and transcript VI mRNA were detected in proximal dendritic processes and in astrocytes. N-methyl-d-aspartate (NMDA) treatment decreased the dendritic label of panBDNF and transcript VI mRNA. In contrast, MK-801 (NMDA antagonist) treatment extended the labeling of all the transcripts in dendrites while K+ depolarization only extended the dendritic labeling of panBDNF and transcript VI mRNAs. These results suggest a NMDA-receptor dependent inhibitory mechanism for dendritic destination of BDNF transcripts in hypothalamic neurons.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  • Aid T, Kazantseva A, Piirsoo M, Palm K, Timmusk T (2007) Mouse and rat BDNF gene structure and expression revisited. J Neurosci Res 85:525–535

    PubMed  Article  CAS  Google Scholar 

  • Aliaga E, Arancibia S, Givalois L, Tapia-Arancibia L (2002) Osmotic stress increases brain-derived neurotrophic factor messenger RNA expression in the hypothalamic supraoptic nucleus with differential regulation of its transcripts: relation to arginine–vasopressin content. Neuroscience 112:841–850

    PubMed  Article  CAS  Google Scholar 

  • An JJ, Gharami K, Liao GY, Woo NH, Lau AG, Vanevski F, Torre ER, Jones KR, Feng Y, Lu B, Xu B (2008) Distinct role of long 3′ UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell 134:175–187

    PubMed  Article  CAS  Google Scholar 

  • Arancibia S, Silhol M, Moulière F, Meffre J, Höllinger I, Maurice T, Tapia-Arancibia L (2008) Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis 31:316–326

    PubMed  Article  CAS  Google Scholar 

  • Arancio O, Chao MV (2007) Neurotrophins, synaptic plasticity and dementia. Curr Opin Neurobiol 17:325–330

    PubMed  Article  CAS  Google Scholar 

  • Batchelor PE, Liberatore GT, Wong JY, Porritt MJ, Frerichs F, Donnan GA, Howells DW (1999) Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci 19:1708–1716

    PubMed  CAS  Google Scholar 

  • Bolton MM, Pittman AJ, Lo DC (2000) Brain-derived neurotrophic factor differentially regulates excitatory and inhibitory synaptic transmission in hippocampal cultures. J Neurosci 20:3221–3232

    PubMed  CAS  Google Scholar 

  • Chiaruttini C, Sonego M, Baj G, Simonato M, Tongiorgi E (2008) BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae. Mol Cell Neurosci 37:11–19

    PubMed  Article  CAS  Google Scholar 

  • Dai X, Qu P, Dreyfus CF (2001) Neuronal signals regulate neurotrophin expression in oligodendrocytes of the basal forebrain. Glia 34:234–239

    PubMed  Article  CAS  Google Scholar 

  • Dougherty KD, Dreyfus CF, Black IB (2000) Brain-derived neurotrophic factor in astrocytes oligodendrocytes and microglia/macrophages after spinal cord injury. Neurobiol Dis 7:574–585

    PubMed  Article  CAS  Google Scholar 

  • Givalois L, Naert G, Tapia-Arancibia L, Arancibia S (2006) Involvement of brain-derived neurotrophic factor in the regulation of hypothalamic somatostatin in vivo. J Endocrinol 188:425–433

    PubMed  Article  CAS  Google Scholar 

  • Guerra-Crespo M, Ubieta R, Joseph-Bravo P, Charli JL, Perez-Martinez L (2001) BDNF increases the early expression of TRH rnRNA in fetal TrkB(+) hypothalamic neurons in primary culture. Eur J Neurosci 14:483–494

    PubMed  Article  CAS  Google Scholar 

  • Halpain S, Hipolito A, Saffer L (1998) Regulation of F-actin stability in dendritic spines by glutamate receptors and calcineurin. J Neurosci 18:9835–9844

    PubMed  CAS  Google Scholar 

  • Kang H, Schuman EM (1996) A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273:1402–1406

    PubMed  Article  CAS  Google Scholar 

  • Katoh-Semba R, Takeuchi IK, Semba R, Kato K (1997) Distribution of brain-derived neurotrophic factor in rats and its changes with development in the brain. J Neurochem 69:34–42

    PubMed  CAS  Article  Google Scholar 

  • Kindler S, Wang H, Richter D, Tiedge H (2005) RNA transport and local control of translation. Annu Rev Cell Dev Biol 21:223–245

    PubMed  Article  CAS  Google Scholar 

  • Kiyama H, Emson PC (1990) Distribution of somatostatin mRNA in the rat nervous system as visualized by a novel non-radioactive in situ hybridization histochemistry procedure. Neuroscience 38:223–244

    PubMed  Article  CAS  Google Scholar 

  • Kokaia Z, Metsis M, Kokaia M, Bengzon J, Elmer E, Smith M-L, Timmusk T, Siesjö BK, Persson H, Lindvall O (1994) Brain insults in rats induce increased expression of the BDNF gene through differential use of multiple promoters. Eur J Neurosci 6:587–596

    PubMed  Article  CAS  Google Scholar 

  • Lauterborn JC, Rivera S, Stinis CT, Hayes VY, Isackson PJ, Gall CM (1996) Differential effects of protein synthesis inhibition on the activity-dependent expression of BDNF transcripts: evidence for immediate-early gene responses from specific promoters. J Neurosci 16:7428–7436

    PubMed  CAS  Google Scholar 

  • Lindholm D, Castrén E, Berzaghi M, Blöchl A, Thoenen H (1994) Activity-dependent and hormonal regulation of neurotrophin mRNA levels in the brain: implications for neuronal plasticity. J Neurobiol 25:1362–1372

    PubMed  Article  CAS  Google Scholar 

  • Lindvall O, Kokaia Z, Bengzon J, Elmér E, Kokaia M (1994) Neurotrophins and brain insults. Trends Neurosci 17:490–496

    PubMed  Article  CAS  Google Scholar 

  • Loudes C, Petit F, Kordon C, Faivre-Bauman A (1999) Distinct populations of hypothalamic dopaminergic neurons exhibit differential responses to brain-derived neurotrophic factor (BDNF) and neurotrophin–3 (NT3). Eur J Neurosci 11:617–624

    PubMed  Article  CAS  Google Scholar 

  • Lu L, Dempsey J, Liu SY, Bossert JM, Shaham Y (2004) A single infusion of brain-derived neurotrophic factor into the ventral tegmental area induces long-lasting potentiation of cocaine seeking after withdrawal. J Neurosci 24:1604–1611

    PubMed  Article  CAS  Google Scholar 

  • Lynch G, Rex CS, Gall CM (2007) LTP consolidation: substrates, explanatory power, and functional significance. Neuropharmacology 52:12–23

    PubMed  Article  CAS  Google Scholar 

  • Marmigère F, Rage F, Tapia-Arancibia L (2001) Regulation of brain-derived neurotrophic factor transcripts by neuronal activation in rat hypothalamic neurons. J Neurosci Res 66:377–389

    PubMed  Article  Google Scholar 

  • Marmigère F, Rage F, Tapia-Arancibia L (2003) GABA-glutamate interaction in the control of BDNF expression in hypothalamic neurons. Neurochem Int 42:353–358

    PubMed  Article  Google Scholar 

  • McAllister AK, Katz LC, Lo DC (1999) Neurotrophins and synaptic plasticity. Annu Rev Neurosci 22:295–318

    PubMed  Article  CAS  Google Scholar 

  • Muslimov IA, Santi E, Homel P, Perini S, Higgins D, Tiedge H (1997) RNA transport in dendrites: a cis-acting targeting element is contained within neuronal BC1 RNA. J Neurosci 17:4722–4733

    PubMed  CAS  Google Scholar 

  • Nawa H, Carnahan J, Gall C (1995) BDNF protein measured by a novel enzyme immunoassay in normal brain and after seizure: partial disagreement with mRNA levels. Eur J Neurosci 7:1527–1535

    PubMed  Article  CAS  Google Scholar 

  • Parés-Herbuté N, Bonet A, Peraldi S, Pin J-P, Gabrion J, Astier H, Tapia-Arancibia L (1988) The presence of non-neuronal cells influences somatostatin release from cultured cerebral cortical cells. Dev Brain Res 40:89–97

    Article  Google Scholar 

  • Pattabiraman PP, Tropea D, Chiaruttini C, Tongiorgi E, Cattaneo A, Domenici L (2005) Neuronal activity regulates the developmental expression and subcellular localization of cortical BDNF mRNA isoforms in vivo. Mol Cell Neurosci 28:556–570

    PubMed  Article  CAS  Google Scholar 

  • Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T (2007) Dissecting the human BDNF locus: bidirectional transcription complex splicing and multiple promoters. Genomics 90:397–406

    PubMed  Article  CAS  Google Scholar 

  • Rage F, Benyassi A, Arancibia S, Tapia-Arancibia L (1992) γ-Aminobutyric acid–glutamate interaction in the control of somatostatin release from hypothalamic neurons in primary culture: in vivo corroboration. Endocrinology 130:1056–1062

    PubMed  Article  CAS  Google Scholar 

  • Rage F, Alonso G, Tapia-Arancibia L (1993) Stimulatory effect of N-methyl-d-aspartate on somatostatin gene expression in cultured hypothalamic neurons. Brain Res Mol Brain Res 17:287–294

    PubMed  Article  CAS  Google Scholar 

  • Rage F, Riteau B, Alonso G, Tapia-Arancibia L (1999) Brain-derived neurotrophic factor and neurotrophin–3 enhance somatostatin gene expression through a likely direct effect on hypothalamic somatostatin neurons. Endocrinology 140:909–916

    PubMed  Article  CAS  Google Scholar 

  • Richter JD, Lorenz LJ (2002) Selective translation of mRNAs at synapses. Curr Opin Neurobiol 12:300–304

    PubMed  Article  CAS  Google Scholar 

  • Righi M, Tongiorgi E, Cattaneo A (2000) Brain-derived neurotrophic factor (BDNF) induces dendritic targeting of BDNF and tyrosine kinase B mRNAs in hippocampal neurons through a phosphatidylinositol–3 kinase-dependent pathway. J Neurosci 20:3165–3174

    PubMed  CAS  Google Scholar 

  • Schinder AF, Poo MM (2000) The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci 23:639–645

    PubMed  Article  CAS  Google Scholar 

  • Schuman EM (1999) mRNA trafficking and local protein synthesis at the synapse. Neuron 23:645–648

    PubMed  Article  CAS  Google Scholar 

  • Simonato M, Bregola G, Armellin M, Del Piccolo P, Rodi D, Zucchini S, Tongiorgi E (2002) Dendritic targeting of mRNAs for plasticity genes in experimental models of temporal lobe epilepsy. Epilepsia 43(Suppl 5):153–158

    PubMed  Article  CAS  Google Scholar 

  • Steward O (1994) Dendrites as compartments for macromolecular synthesis. Proc Natl Acad Sci USA 91:10766–10768

    PubMed  Article  CAS  Google Scholar 

  • Steward O (1997) mRNA localization in neurons: a multipurpose mechanism? Neuron 18:9–12

    PubMed  Article  CAS  Google Scholar 

  • Steward O, Falk PM, Torre ER (1996) Ultrastructural basis for gene expression at the synapse: synapse-associated polyribosome complexes. J Neurocytol 25:717–734

    PubMed  Article  CAS  Google Scholar 

  • Steward O, Wallace CS, Lyford GL, Worley PF (1998) Synaptic activation causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on dendrites. Neuron 21:741–751

    PubMed  Article  CAS  Google Scholar 

  • Tanaka J, Horiike Y, Matsuzaki M, Miyazaki T, Ellis-Davies GC, Kasai H (2008) Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319:1683–1687

    PubMed  Article  CAS  Google Scholar 

  • Tapia-Arancibia L, Rage F, Givalois L, Arancibia S (2004) Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 25:77–107

    PubMed  Article  CAS  Google Scholar 

  • Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S (2008) New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Res Rev 59:201–220

    PubMed  Article  CAS  Google Scholar 

  • Thoenen H (2000) Neurotrophins and activity-dependent plasticity. Prog Brain Res 128:183–191

    PubMed  Article  CAS  Google Scholar 

  • Timmusk T, Palm K, Metsis M, Reintam T, Paalme V, Saarma M, Persson H (1993) Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron 10:475–489

    PubMed  Article  CAS  Google Scholar 

  • Tongiorgi E, Righi M, Cattaneo A (1997) Activity-dependent dendritic targeting of BDNF and TrkB mRNAs in hippocampal neurons. J Neurosci 17:9492–9505

    PubMed  CAS  Google Scholar 

  • Tongiorgi E, Armellin M, Giulianini PG, Bregola G, Zucchini S, Paradiso B, Steward O, Cattaneo A, Simonato M (2004) Brain-derived neurotrophic factor mRNA and protein are targeted to discrete dendritic laminas by events that trigger epileptogenesis. J Neurosci 24:6842–6852

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a ECOS-Sud network grant to E. Aliaga and L. Tapia-Arancibia and by grants from FONDECYT-Chile (#1040306) and DIPUV(15/2006, CI-1-2006) to E. Aliaga We also thank Mr. Edmond Savary for his valuable technical help.

Author information

Affiliations

  1. Centro de Neurobiología y Plasticidad del Desarrollo, Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Gran Bretaña 1111, Playa Ancha, Valparaiso, Chile

    Esteban Enrique Aliaga & I. Mendoza

  2. U710, Inserm, 34095, Montpellier, France

    L. Tapia-Arancibia

  3. Univ Montpellier 2, 34095, Montpellier, France

    L. Tapia-Arancibia

  4. EPHE, 75007, Paris, France

    L. Tapia-Arancibia

Authors
  1. Esteban Enrique Aliaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Mendoza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Tapia-Arancibia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Esteban Enrique Aliaga.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Aliaga, E.E., Mendoza, I. & Tapia-Arancibia, L. Distinct subcellular localization of BDNF transcripts in cultured hypothalamic neurons and modification by neuronal activation. J Neural Transm 116, 23–32 (2009). https://doi.org/10.1007/s00702-008-0159-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-008-0159-8

Keywords

  • Dendritic mRNA
  • BDNF
  • BDNF exon
  • In situ hybridization
  • Hypothalamic neurons