Elsevier

Brain Research

Volume 633, Issues 1–2, 7 January 1994, Pages 189-196
Brain Research

Research report
Chronic 1,25-dihydroxyvitamin D3-mediated induction of nerve growth factor mRNA and protein in L929 fibroblasts and in adult rat brain

https://doi.org/10.1016/0006-8993(94)91539-3Get rights and content

Abstract

We have proposed that elevating levels of nerve growth factor (NGF) in the CNS is a rational strategy for treating certain neurodegenerative disorders. The present studies were conducted to determine: (1) if pharmacologically induced levels of NGF could be sustained for an extended time, and (2) if correlations exist between increases in NGF mRNA and NGF protein in L929 cells and in vivo. Short-term treatment of L929 cells with 1,25-dihydroxyvitamin D3 resulted in a two-fold increase in both NGF mRNA and NGF protein. These increases were sustained for up to 48 h with continuous exposure to 1,25-dihydroxyvitamin D3. In rats, 1,25-dihydroxyvitamin D3 (2.5 nmol; i.c.v.) induced NGF mRNA transiently, with peak two-fold increased observed 4 h post-injection. In contrast to L929 cells, 1,25-dihydroxyvitamin D3 did not elicit an increase in NGF protein after a single administration in vivo. However, consistent with long-term exposure in L929 cells, chronic 6 day infusion of 1,25-dihydroxyvitamin D3 resulted in induction of both NGF mRNA and NGF protein in the brain. These results indicate that 1,25-dihydroxyvitamin D3-mediated NGF induction in cultured L929 cells may predict of NGF induction in vivo, suggesting that L929 cells may have utility in studying underlying mechanisms of NGF induction by 1,25-dihydroxyvitamin D3. On the basis of NGF's ability to increase cholinergic function in animal models of cholinergic degeneration, these results are supportive of a role for NGF inducers as potential drugs for neurodegenerative disorders.

References (46)

  • HaggT. et al.

    Nerve growth factor (NGF) reverses axotomy-induced decreases in choline-acetyltransferase, NGF-receptor and size of medial septum cholinergic neurons

    Brain Res.

    (1989)
  • HigginsG.A. et al.

    NGF induction of NGF receptor gene expression and cholinergic neuronal hypertrophy within the basal forebrain of the adult rat

    Neuron

    (1989)
  • LapchakP. et al.

    Effect of recombinant human nerve growth factor on presynaptic cholinergic function in rat hippocampal slices following partial septo-hippocampal lesions: measures of ACh synthesis and release

    Neuroscience

    (1991)
  • LuB. et al.

    Expression of NGF and NGF receptor mRNA's in the developing brain: evidence for local delivery and action of NGF

    Exp. Neurol.

    (1989)
  • MandelR.J. et al.

    Spatial learning in rats: correlation with correlation with cortical choline acetltransferase and improvement with NGF following NBM damage

    Exp. Neurol.

    (1989)
  • MobleyW.C. et al.

    Nerve growth factor increases choline acetyltransferase activity in developing basal forebrain neurons

    Mol. Brain Res.

    (1986)
  • SaporitoM.S. et al.

    Pharmacological induction of nerve growth factor mRNA in adult rat brain

    Exp. Neurol.

    (1993)
  • ThoenenH.

    The changing scene of neurotrophic factors

    (1991)
  • YoshidaK. et al.

    Fibroblast growth factors stimulate nerve growth factor synthesis and secretion by astrocytes

    Brain Res.

    (1991)
  • Ayer-LelievreC. et al.

    Expression of the β-nerve growth factor gene in hippocampal neurons

    Science

    (1988)
  • Carman-KrzanM. et al.

    Regulation by interleukin 1 of nerve growth factor secretion and nerve growth factor mRNA expression in rat primary astroglial cultures

    J. Neurochem.

    (1991)
  • DarwishH.M. et al.

    Identification of a 1,25-dihydroxyvitamin D3-response element in the 5′ flanking region of the rat calbindin D-9K gene

  • DemayM.B. et al.

    DNA sequences in the rat osteocalcin gene that bind the 1,25-dihydroxyvitamin D3 receptor and confer responsiveness to 1,25-dihydroxyvitamin D D3

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