Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors

Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors Neurotrophins and other neurotrophic factors have been shown to support the survival and differentiation of many neuronal populations of the central and peripheral nervous system. Therefore, administering neurotrophic factors could represent an alternative strategy for the treatment of acute and chronic brain disorders. However, the delivery of neurotrophic factors to the brain is one of the largest obstacles in the development of effective therapy for neurodegenerative disorders, because these proteins are not able to cross the blood–brain barrier. The induction of growth factor synthesis in the brain tissue by systemically administered lipophilic drugs, such as β-adrenoceptor agonists, shown to increase endogenous nerve growth factor (NGF) synthesis in the brain, would be an elegant way to overcome these problems of application. Stimulation of β-adrenoceptors with clenbuterol led to increased NGF synthesis in cultured central nervous system (CNS) cells and rat brain tissue. Clenbuterol-induced NGF expression was reduced to the control levels by coadministration of β-adrenoceptor antagonist propranolol. Furthermore, clenbuterol protected rat hippocampal neurons subjected to excitotoxic damage. The neuroprotective effect of clenbuterol in vitro depended on increased NGF synthesis, since the neuroprotection was abolished by NGF antisense oligonucleotide as well as by antibodies directed against NGF itself. In vivo, clenbuterol protected rat hippocampus in a model of transient forebrain ischemia and reduced the infarct volume in a rat model of permanent middle cerebral artery occlusion (MCAo). The neuroprotective effect of clenbuterol in vivo was accompanied by enhanced NGF synthesis in brain tissue. These findings support our hypothesis that orally active NGF inducers may have a potential as therapeutic agents for the treatment of neurodegenerative disorders and stroke. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Reviews Elsevier

Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors

Brain Research Reviews, Volume 30 (2) – Aug 1, 1999

Loading next page...
 
/lp/elsevier/neuroprotection-mediated-via-neurotrophic-factors-and-induction-of-eMtD6TNT0z
Publisher
Elsevier
Copyright
Copyright © 1999 Elsevier Science B.V.
ISSN
0165-0173
D.O.I.
10.1016/S0165-0173(99)00013-2
Publisher site
See Article on Publisher Site

Abstract

Neurotrophins and other neurotrophic factors have been shown to support the survival and differentiation of many neuronal populations of the central and peripheral nervous system. Therefore, administering neurotrophic factors could represent an alternative strategy for the treatment of acute and chronic brain disorders. However, the delivery of neurotrophic factors to the brain is one of the largest obstacles in the development of effective therapy for neurodegenerative disorders, because these proteins are not able to cross the blood–brain barrier. The induction of growth factor synthesis in the brain tissue by systemically administered lipophilic drugs, such as β-adrenoceptor agonists, shown to increase endogenous nerve growth factor (NGF) synthesis in the brain, would be an elegant way to overcome these problems of application. Stimulation of β-adrenoceptors with clenbuterol led to increased NGF synthesis in cultured central nervous system (CNS) cells and rat brain tissue. Clenbuterol-induced NGF expression was reduced to the control levels by coadministration of β-adrenoceptor antagonist propranolol. Furthermore, clenbuterol protected rat hippocampal neurons subjected to excitotoxic damage. The neuroprotective effect of clenbuterol in vitro depended on increased NGF synthesis, since the neuroprotection was abolished by NGF antisense oligonucleotide as well as by antibodies directed against NGF itself. In vivo, clenbuterol protected rat hippocampus in a model of transient forebrain ischemia and reduced the infarct volume in a rat model of permanent middle cerebral artery occlusion (MCAo). The neuroprotective effect of clenbuterol in vivo was accompanied by enhanced NGF synthesis in brain tissue. These findings support our hypothesis that orally active NGF inducers may have a potential as therapeutic agents for the treatment of neurodegenerative disorders and stroke.

Journal

Brain Research ReviewsElsevier

Published: Aug 1, 1999

References

  • Cyclic AMP-mediated induction of the glial fibrillary acidic protein is independent of protein kinase A activation in rat C6 glioma
    Anciaux, K.; van Dommelen, K.; Nikolai, S.; van Mechelen, E.
  • Induction of c- fos and TIS genes in cultured astrocytes by neurotransmitters
    Arenander, A.T.; de Vellis, J.; Herschman, H.R.
  • Regulation by interleukin-1 of nerve growth factor secretion and nerve growth factor mRNA expression in rat primary astroglial cultures
    Carman-Krzan, M.; Vige, X.; Wise, B.C.
  • Rat ciliary neurotrophic factor (CNTF): gene structure and regulation of mRNA levels in glial cell cultures
    Carroll, P.; Sendtner, M.; Meyer, M.; Thoenen, H.
  • Induction of nerve growth factor gene expression by 12- O -tetradecanoyl phorbol 13-acetate
    D'Mello, S.R.; Heinrich, G.
  • Regulation of nerve growth factor secretion and mRNA expression by bacterial lipopolysaccharide in primary cultures of rat astrocytes
    Galve-Roperh, I.; Malpartida, J.M.; Haro, A.; Brachet, P.; Diaz-Laviada, I.
  • Interleukin 1 of the central nervous system is produced by ameboid microglia
    Giulian, D.; Baker, T.J.; Shih, L.C.; Lachman, L.B.
  • Phorbol ester-induced change in astrocyte morphology: correlation with protein kinase C activation and protein phosphorylation
    Harrison, B.C.; Mobley, P.L.
  • Induction of nerve growth factor and basic fibroblast growth factor mRNA following clenbuterol: contrasting anatomical and cellular localization
    Hayes, V.Y.; Isackson, P.J.; Fabrazzo, M.; Follesa, P.; Mocchetti, I.
  • Secretion of nerve growth factor in cultures of glial cells and neurons derived from different regions of the mouse brain
    Houlgatte, R.; Mallat, M.; Brachet, P.; Prochiantz, A.
  • Ciliary neurotrophic factor enhances the survival of Purkinje cells in vitro
    Lärkfors, L.; Lindsay, R.M.; Alderson, R.F.
  • Differential regulation of NGF synthesis in neurons and astrocytes by glucocorticoid hormones
    Lindholm, D.; Castren, E.; Hengerer, B.; Zafra, F.; Berninger, B.; Thoenen, H.
  • Theoretical basis for a pharmacology of nerve growth biosynthesis
    Mocchetti, I.
  • Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes
    Rudge, J.S.; Li, Y.; Pasnikowski, E.M.; Mattson, K.; Pan, L.; Yancopoulos, G.D.; Wiegand, S.J.; Lindsay, R.M.; Ip, N.Y.
  • Clenbuterol protects mouse cerebral cortex and rat hippocampus from ischemic damage and attenuates glutamate neurotoxicity in cultured hippocampal neurons by induction of NGF
    Semkova, I.; Schilling, M.; Henrich-Noack, P.; Rami, A.; Krieglstein, J.
  • Plasticity of astrocytes
    Shao, Y.; McCarthy, K.D.
  • Expression of adrenergic receptors in individual astrocytes and motor neurons isolated from the adult rat brain
    Shao, Y.; Sutin, J.
  • Role of cholinergic system in the regulation of neurotrophin synthesis
    Yu, J.; Pizzo, D.P.; Hutton, L.A.; Perez-Polo, R.J.
  • Altered NGF protein levels in different brain areas after immunolesion
    Yu, J.; Wiley, R.G.; Perez-Polo, R.J.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off