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EMBO J. Nov 1990; 9(11): 3545–3550.
PMCID: PMC552104

Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors.


The mRNAs of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) exhibit a similar, though not identical, regional and cellular distribution in the rodent brain. In situ hybridization experiments have shown that BDNF, like NGF, is predominantly expressed by neurons. The neuronal localization of the mRNAs of these two neurotrophic molecules raised the question as to whether neuronal activity might be involved in the regulation of their synthesis. After we had demonstrated that depolarization with high potassium (50 mM) resulted in an increase in the levels of both BDNF and NGF mRNAs in cultures of hippocampal neurons, we investigated the effect of a large number of transmitter substances. Kainic acid, a glutamate receptor agonist, was by far the most effective in increasing BDNF and NGF mRNA levels in the neurons, but neither N-methyl-D-aspartic acid (NMDA) nor inhibitors of the NMDA glutamate receptors had any effect. However, the kainic acid mediated increase was blocked by antagonists of non-NMDA receptors. Kainic acid also elevated levels of BDNF and NGF mRNAs in rat hippocampus and cortex in vivo. These results suggest that the synthesis of these two neurotrophic factors in the brain is regulated by neuronal activity via non-NMDA glutamate receptors.

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Selected References

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  • Ayer-LeLievre C, Olson L, Ebendal T, Seiger A, Persson H. Expression of the beta-nerve growth factor gene in hippocampal neurons. Science. 1988 Jun 3;240(4857):1339–1341. [PubMed]
  • Bandtlow CE, Heumann R, Schwab ME, Thoenen H. Cellular localization of nerve growth factor synthesis by in situ hybridization. EMBO J. 1987 Apr;6(4):891–899. [PMC free article] [PubMed]
  • Barde YA. Trophic factors and neuronal survival. Neuron. 1989 Jun;2(6):1525–1534. [PubMed]
  • Barth EM, Korsching S, Thoenen H. Regulation of nerve growth factor synthesis and release in organ cultures of rat iris. J Cell Biol. 1984 Sep;99(3):839–843. [PMC free article] [PubMed]
  • Brewer GJ, Cotman CW. Survival and growth of hippocampal neurons in defined medium at low density: advantages of a sandwich culture technique or low oxygen. Brain Res. 1989 Aug 7;494(1):65–74. [PubMed]
  • Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988 Oct;1(8):623–634. [PubMed]
  • Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neurotoxicity in cortical cell culture. J Neurosci. 1987 Feb;7(2):357–368. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Clegg DO, Large TH, Bodary SC, Reichardt LF. Regulation of nerve growth factor mRNA levels in developing rat heart ventricle is not altered by sympathectomy. Dev Biol. 1989 Jul;134(1):30–37. [PubMed]
  • Cole AJ, Saffen DW, Baraban JM, Worley PF. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature. 1989 Aug 10;340(6233):474–476. [PubMed]
  • Davies AM, Bandtlow C, Heumann R, Korsching S, Rohrer H, Thoenen H. Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature. 326(6111):353–358. [PubMed]
  • Ebendal T, Olson L, Seiger A. The level of nerve growth factor (NGF) as a function of innervation. A correlation radio-immunoassay and bioassay study of the rat iris. Exp Cell Res. 1983 Oct 15;148(2):311–317. [PubMed]
  • Furukawa S, Furukawa Y, Satoyoshi E, Hayashi K. Synthesis/secretion of nerve growth factor is associated with cell growth in cultured mouse astroglial cells. Biochem Biophys Res Commun. 1987 Jan 30;142(2):395–402. [PubMed]
  • Gall CM, Isackson PJ. Limbic seizures increase neuronal production of messenger RNA for nerve growth factor. Science. 1989 Aug 18;245(4919):758–761. [PubMed]
  • Hellweg R, Bandtlow CE, Heumann R, Korsching S. Nerve growth factor synthesis in cultured rat iris: modulation by endogenous transmitter substances. Exp Cell Res. 1988 Nov;179(1):18–30. [PubMed]
  • Hengerer B, Lindholm D, Heumann R, Rüther U, Wagner EF, Thoenen H. Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. Proc Natl Acad Sci U S A. 1990 May;87(10):3899–3903. [PMC free article] [PubMed]
  • Heumann R, Thoenen H. Comparison between the time course of changes in nerve growth factor protein levels and those of its messenger RNA in the cultured rat iris. J Biol Chem. 1986 Jul 15;261(20):9246–9249. [PubMed]
  • Heumann R, Korsching S, Scott J, Thoenen H. Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues. EMBO J. 1984 Dec 20;3(13):3183–3189. [PMC free article] [PubMed]
  • Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde YA. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J. 1990 Aug;9(8):2459–2464. [PMC free article] [PubMed]
  • Johnson JE, Barde YA, Schwab M, Thoenen H. Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. J Neurosci. 1986 Oct;6(10):3031–3038. [PubMed]
  • Korsching S, Thoenen H. Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3513–3516. [PMC free article] [PubMed]
  • Korsching S, Thoenen H. Treatment with 6-hydroxydopamine and colchicine decreases nerve growth factor levels in sympathetic ganglia and increases them in the corresponding target tissues. J Neurosci. 1985 Apr;5(4):1058–1061. [PubMed]
  • Korsching S, Auburger G, Heumann R, Scott J, Thoenen H. Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J. 1985 Jun;4(6):1389–1393. [PMC free article] [PubMed]
  • Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989 Sep 14;341(6238):149–152. [PubMed]
  • Lindholm D, Heumann R, Hengerer B, Thoenen H. Interleukin 1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts. J Biol Chem. 1988 Nov 5;263(31):16348–16351. [PubMed]
  • Lindsay RM. Adult rat brain astrocytes support survival of both NGF-dependent and NGF-insensitive neurones. Nature. 1979 Nov 1;282(5734):80–82. [PubMed]
  • Lindsay RM, Thoenen H, Barde YA. Placode and neural crest-derived sensory neurons are responsive at early developmental stages to brain-derived neurotrophic factor. Dev Biol. 1985 Dec;112(2):319–328. [PubMed]
  • McGeer EG, McGeer PL, Singh K. Kainate-induced degeneration of neostriatal neurons: dependency upon corticostriatal tract. Brain Res. 1978 Jan 13;139(2):381–383. [PubMed]
  • Monaghan DT, Bridges RJ, Cotman CW. The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol. 1989;29:365–402. [PubMed]
  • Rennert PD, Heinrich G. Nerve growth factor mRNA in brain: localization by in situ hybridization. Biochem Biophys Res Commun. 1986 Jul 31;138(2):813–818. [PubMed]
  • Rodriguez-Tébar A, Jeffrey PL, Thoenen H, Barde YA. The survival of chick retinal ganglion cells in response to brain-derived neurotrophic factor depends on their embryonic age. Dev Biol. 1989 Dec;136(2):296–303. [PubMed]
  • Rohrer H, Heumann R, Thoenen H. The synthesis of nerve growth factor (NGF) in developing skin is independent of innervation. Dev Biol. 1988 Jul;128(1):240–244. [PubMed]
  • Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, et al. Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family. Nature. 1987 Jul 16;328(6127):221–227. [PubMed]
  • Shelton DL, Reichardt LF. Expression of the beta-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7951–7955. [PMC free article] [PubMed]
  • Shelton DL, Reichardt LF. Studies on the expression of the beta nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2714–2718. [PMC free article] [PubMed]
  • Spranger Matthias, Lindholm Dan, Bandtlow Christine, Heumann Rolf, Gnahn Hannes, Näher-Noé Martina, Thoenen Hans. Regulation of Nerve Growth Factor (NGF) Synthesis in the Rat Central Nervous System: Comparison between the Effects of Interleukin-1 and Various Growth Factors in Astrocyte Cultures and in vivo. Eur J Neurosci. 1990 Jan;2(1):69–76. [PubMed]
  • Wang AM, Doyle MV, Mark DF. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9717–9721. [PMC free article] [PubMed]
  • Whittemore SR, Ebendal T, Lärkfors L, Olson L, Seiger A, Strömberg I, Persson H. Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. Proc Natl Acad Sci U S A. 1986 Feb;83(3):817–821. [PMC free article] [PubMed]
  • Whittemore SR, Friedman PL, Larhammar D, Persson H, Gonzalez-Carvajal M, Holets VR. Rat beta-nerve growth factor sequence and site of synthesis in the adult hippocampus. J Neurosci Res. 1988 Aug;20(4):403–410. [PubMed]

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