Role of nerve growth factor in the expression of trkA mRNA in cultured embryonic rat basal forebrain cholinergic neurons

Using a quantitative reverse transcription‐polymerase chain reaction (RT‐PCR), we studied the regulation of trkA mRNA expression in serum‐free, cultured basal forebrain neurons from 17‐day fetal rats. Besides increasing choline acetyltransferase (ChAT) activities, nerve growth factor (NGF) strikingly induced trkA gene expression in a time‐ and NGF concentrationdependent manner. Therefore, NGF might play a critical role in trkA gene expression during the development of basal forebrain cholinergic neurons. Furthermore, to investigate whether this up‐regulation is connected with the trophic effects on basal forebrain cholinergic neurons, we examined the effects of some other neurotrophic agents (BDNF, NT‐3, bFGF, CNTF, and 40 mM KCl) upon ChAT activity and trkA gene expression. Some neurotrophic factors increased ChAT activities to the same degree as NGF, whereas they did not stimulate trkA mRNA expression so potently. NT‐3 plus K252b promotes the tyrosine phosphorylation of TrkA in PC12 cells and increases ChAT activity in cultured basal forebrain cholinergic neurons like NGF (Knusel et al., J Neurochem 59: 715–722, 1992). W e found that NT‐3 plus K252b upregulated the level of trkA mRNA. These results suggested that the expression of trkA mRNA is regulated directly by its specific ligand NGF, rather than neurotrophic effects upon basal forebrain cholinergic neurons and that the up‐regulation is connected to a molecular event initiated by the binding of NGF to the TrkA receptor. ©1995 Wiley‐Liss, Inc.

[1]  S. Furukawa,et al.  [Neurotrophins and their receptors]. , 1997, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[2]  H. Hatanaka,et al.  Cultured basal forebrain cholinergic neurons from postnatal rats show both overlapping and non-overlapping responses to the neurotrophins , 1995, Brain Research.

[3]  H. Hatanaka,et al.  High potassium and cyclic AMP analog promote neuronal survival of basal forebrain cholinergic neurons in culture from postnatal 2-week-old rats. , 1994, Brain research. Developmental brain research.

[4]  D. Pfaff,et al.  In situ hybridization detection of trka mRNA in brain: Distribution, colocalization with p75NGFR and up‐regulation by nerve growth factor , 1994, The Journal of comparative neurology.

[5]  T. Ikeuchi,et al.  Nerve growth factor induces trkA mRNA expression in cultured basal forebrain cholinergic neurons from 17-day fetal rats , 1994, Neuroscience Letters.

[6]  A. Davies,et al.  Regulation of expression of mRNAs encoding the nerve growth factor receptors p75 and trkA in developing sensory neurons. , 1993, Development.

[7]  R. Jaenisch,et al.  p75-Deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins , 1993, Neuron.

[8]  S. Korsching,et al.  The neurotrophic factor concept: a reexamination , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  K. Mikoshiba,et al.  Basic fibroblast growth factor rescues CNS neurons from cell death caused by high oxygen atmosphere in culture , 1992, Brain Research.

[10]  T. Ikeuchi,et al.  Nerve growth factor (NGF)-mediated up-regulation of low-affinity NGF receptor gene expression in cultured basal forebrain cholinergic neurons from postnatal 3-day-old rats. , 1992, Brain research. Molecular brain research.

[11]  B. Hempstead,et al.  Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor-induced differentiation , 1992, Neuron.

[12]  D. Kaplan,et al.  Neurotrophin-induced trk receptor phosphorylation and cholinergic neuron response in primary cultures of embryonic rat brain neurons. , 1992, Neuroreport.

[13]  Joseph B. Long,et al.  p140 trk mRNA marks NGF-responsive forebrain neurons: Evidence that trk gene expression is induced by NGF , 1992, Neuron.

[14]  D. Kaplan,et al.  K‐252b Selectively Potentiates Cellular Actions and trk Tyrosine Phosphorylation Mediated by Neurotrophin‐3 , 1992, Journal of neurochemistry.

[15]  H. Hatanaka,et al.  Neurotrophic effect of brain-derived neurotrophic factor on basal forebrain cholinergic neurons in culture from postnatal rats , 1992, Neuroscience Research.

[16]  D. Anderson,et al.  Membrane depolarization induces p140trk and NGF responsiveness, but not p75LNGFR, in MAH cells. , 1992, Science.

[17]  R. Jaenisch,et al.  Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system , 1992, Cell.

[18]  E. Shooter,et al.  The rat trk protooncogene product exhibits properties characteristic of the slow nerve growth factor receptor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. Varon,et al.  Ciliary neurotrophic factor prevents neuronal degeneration and promotes low affinity NGF receptor expression in the adult rat CNS , 1992, Neuron.

[20]  N. Panayotatos,et al.  Ciliary neurotrophic factor enhances neuronal survival in embryonic rat hippocampal cultures , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  F. Hefti,et al.  Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H. Thoenen,et al.  Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non‐NMDA glutamate receptors. , 1990, The EMBO journal.

[23]  Yves-Alain Barde,et al.  Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture , 1990, Neuron.

[24]  J. Schwaber,et al.  Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  F. Hefti,et al.  Development of septal cholinergic neurons in culture: plating density and glial cells modulate effects of NGF on survival, fiber growth, and expression of transmitter-specific enzymes , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  C. Cotman,et al.  Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo , 1988, Nature.

[27]  H. Hatanaka,et al.  Developmental change in the nerve growth factor action from induction of choline acetyltransferase to promotion of cell survival in cultured basal forebrain cholinergic neurons from postnatal rats. , 1988, Brain research.

[28]  H. Thoenen,et al.  Developmental changes of nerve growth factor and its mRNA in the rat hippocampus: comparison with choline acetyltransferase. , 1987, Developmental biology.

[29]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[30]  T. Maeda,et al.  Visualization of detailed acetylcholinesterase fiber and neuron staining in rat brain by a sensitive histochemical procedure. , 1986, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[31]  F. Hefti,et al.  Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  R. Riopelle,et al.  Distribution of neuronal receptors for nerve growth factor in the rat , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  H. Thoenen,et al.  Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. , 1985, The EMBO journal.

[34]  M. Schwab,et al.  NGF-mediated increase of choline acetyltransferase (ChAT) in the neonatal rat forebrain: evidence for a physiological role of NGF in the brain? , 1983, Brain research.

[35]  D. Amaral,et al.  An anatomical study of the development of the septo-hippocampal projection in the rat. , 1983, Brain research.

[36]  R. Levi‐montalcini,et al.  Nerve growth factor. , 1975, Science.

[37]  F. Fonnum,et al.  A rapid radiochemical method for the determination of choline acetyltransferase , 1975, Journal of neurochemistry.

[38]  V. Bocchini,et al.  The nerve growth factor: purification as a 30,000-molecular-weight protein. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[39]  C. Altar,et al.  Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain. , 1991, Proceedings of the National Academy of Sciences of the United States of America.