The second messenger, cyclic AMP, is not sufficient for myelin gene induction in the peripheral nervous system

J. F. Poduslo, R. S. Walikonis, M. C. Domec, C. T. Berg, C. J. Holtz-Heppelmann

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The adenylyl cyclase-cyclic AMP (cAMP) second messenger pathway has been proposed to regulate myelin gone expression; however, a clear correlation between endogenous cAMP levels and myelin-specific mRNA levels has never been demonstrated during the induction or maintenance of differentiation by the myelinating Schwann cell. Endogenous cAMP levels decreased to 8-10% of normal nerve by 3 days after crush or permanent transaction injury of adult rat sciatic nerve. Whereas levels remained low after transaction injury, cAMP levels reached only 27% of the normal values by 35 days after crush injury. Because P0 mRNA levels were 60% of normal levels by 14 days and 100% by 21 days after crush injury, cAMP increased only well after P0 gene induction. cAMP, therefore, does not appear to trigger myelin gene induction but may be involved in myelin assembly or maintenance. Forskolin, an activator of adenylyl cyclase, increased endoneurial cAMP levels only in the normal nerve, and in the crushed nerve beginning at 16 days after injury, but at no time in the transected nerve. Only by treating transacted nerve with 3-isobutyl-1- methylxanthine (IBMX), an inhibitor of cAMP phosphodiesterases, in combination with forskolin was it possible to increase cAMP levels. No induction of myelin genes, however, was observed with short- or long-term treatment with IBMX and forskolin in the transected nerve. A threefold increase in phosphodiesterase activity was observed at 35 days after both injuries, and a nonmyelinated nerve was shown to have even higher activity. These experiments, therefore, suggest an important role for phosphodiesterase in the inactivation of this second messenger-dependent stimuli when Schwann cells are nonmyelinating, such as after sciatic nerve injury or in the nonmyelinated nerve, which again implies that cAMP may be required for the maintenance of the myelin sheath.

Original languageEnglish (US)
Pages (from-to)149-159
Number of pages11
JournalJournal of Neurochemistry
Volume65
Issue number1
StatePublished - 1995

Fingerprint

Peripheral Nervous System
Neurology
Second Messenger Systems
Myelin Sheath
Cyclic AMP
Genes
Phosphoric Diester Hydrolases
Colforsin
Wounds and Injuries
Schwann Cells
Maintenance
Sciatic Nerve
Adenylyl Cyclases
Cells
1-Methyl-3-isobutylxanthine
Messenger RNA
Rats
Reference Values

Keywords

  • 3-Isobutyl-1-methylxanthine
  • Crush injury
  • Cyclic AMP
  • Myelin gene induction
  • Rat sciatic nerve
  • Schwann cell
  • Transected nerve

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Poduslo, J. F., Walikonis, R. S., Domec, M. C., Berg, C. T., & Holtz-Heppelmann, C. J. (1995). The second messenger, cyclic AMP, is not sufficient for myelin gene induction in the peripheral nervous system. Journal of Neurochemistry, 65(1), 149-159.

The second messenger, cyclic AMP, is not sufficient for myelin gene induction in the peripheral nervous system. / Poduslo, J. F.; Walikonis, R. S.; Domec, M. C.; Berg, C. T.; Holtz-Heppelmann, C. J.

In: Journal of Neurochemistry, Vol. 65, No. 1, 1995, p. 149-159.

Research output: Contribution to journalArticle

Poduslo, JF, Walikonis, RS, Domec, MC, Berg, CT & Holtz-Heppelmann, CJ 1995, 'The second messenger, cyclic AMP, is not sufficient for myelin gene induction in the peripheral nervous system', Journal of Neurochemistry, vol. 65, no. 1, pp. 149-159.
Poduslo, J. F. ; Walikonis, R. S. ; Domec, M. C. ; Berg, C. T. ; Holtz-Heppelmann, C. J. / The second messenger, cyclic AMP, is not sufficient for myelin gene induction in the peripheral nervous system. In: Journal of Neurochemistry. 1995 ; Vol. 65, No. 1. pp. 149-159.
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AB - The adenylyl cyclase-cyclic AMP (cAMP) second messenger pathway has been proposed to regulate myelin gone expression; however, a clear correlation between endogenous cAMP levels and myelin-specific mRNA levels has never been demonstrated during the induction or maintenance of differentiation by the myelinating Schwann cell. Endogenous cAMP levels decreased to 8-10% of normal nerve by 3 days after crush or permanent transaction injury of adult rat sciatic nerve. Whereas levels remained low after transaction injury, cAMP levels reached only 27% of the normal values by 35 days after crush injury. Because P0 mRNA levels were 60% of normal levels by 14 days and 100% by 21 days after crush injury, cAMP increased only well after P0 gene induction. cAMP, therefore, does not appear to trigger myelin gene induction but may be involved in myelin assembly or maintenance. Forskolin, an activator of adenylyl cyclase, increased endoneurial cAMP levels only in the normal nerve, and in the crushed nerve beginning at 16 days after injury, but at no time in the transected nerve. Only by treating transacted nerve with 3-isobutyl-1- methylxanthine (IBMX), an inhibitor of cAMP phosphodiesterases, in combination with forskolin was it possible to increase cAMP levels. No induction of myelin genes, however, was observed with short- or long-term treatment with IBMX and forskolin in the transected nerve. A threefold increase in phosphodiesterase activity was observed at 35 days after both injuries, and a nonmyelinated nerve was shown to have even higher activity. These experiments, therefore, suggest an important role for phosphodiesterase in the inactivation of this second messenger-dependent stimuli when Schwann cells are nonmyelinating, such as after sciatic nerve injury or in the nonmyelinated nerve, which again implies that cAMP may be required for the maintenance of the myelin sheath.

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