Bone morphogenetic proteins and neurotrophins provide complementary protection of septal cholinergic function during phosphatase inhibitor-induced stress

Doris Nonner, Kiran Panickar, Ellen Barrett, John Barrett

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cultures of embryonic rat septum were exposed for 24-48 h to 2-5 nM okadaic acid (OA), an inhibitor of pp1A and pp2A phosphatases. This stress killed approximately 75% of neurons. A neurotrophin (NT) combination (nerve growth factor and brain-derived neurotrophic factor, each 100 ng/mL) plus a bone morphogenetic protein (BMP6 or BMP7, 5 nM) reduced the death of both cholinergic and non-cholinergic neurons, and preserved choline acetyltransferase (ChAT) activity assayed 2-6 days post-stress. This NT + BMP combination preserved ChAT activity better than either NTs or BMPs alone, and was effective even if trophic factor addition was delayed until 12 h after stress onset. A general caspase inhibitor (qVD-OPH, 10 μg/mL) also increased survival of stressed cholinergic neurons, but its protection of ChAT activity was shorter lived than that produced by the NT + BMP combination. Neither the NT + BMP combination nor the caspase inhibitor reduced the OA-induced increase in tau phosphorylation. These findings indicate that NTs and BMPs have synergistic protective effects against an OA stress, and suggest that at least some of these protective effects occur upstream of caspase activation.

Original languageEnglish
Pages (from-to)77-87
Number of pages11
JournalJournal of Neurochemistry
Volume91
Issue number1
DOIs
StatePublished - Oct 1 2004

Fingerprint

Bone Morphogenetic Proteins
Nerve Growth Factors
Phosphoric Monoester Hydrolases
Okadaic Acid
Cholinergic Agents
Choline O-Acetyltransferase
Neurons
Caspase Inhibitors
Phosphorylation
Cholinergic Neurons
Brain-Derived Neurotrophic Factor
Nerve Growth Factor
Caspases
Rats
Chemical activation

Keywords

  • Apoptosis
  • Bone morphogenetic protein
  • Choline acetyltransferase
  • Cholinergic neuron
  • Neurotrophins
  • Okadaic acid

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Bone morphogenetic proteins and neurotrophins provide complementary protection of septal cholinergic function during phosphatase inhibitor-induced stress",
abstract = "Cultures of embryonic rat septum were exposed for 24-48 h to 2-5 nM okadaic acid (OA), an inhibitor of pp1A and pp2A phosphatases. This stress killed approximately 75{\%} of neurons. A neurotrophin (NT) combination (nerve growth factor and brain-derived neurotrophic factor, each 100 ng/mL) plus a bone morphogenetic protein (BMP6 or BMP7, 5 nM) reduced the death of both cholinergic and non-cholinergic neurons, and preserved choline acetyltransferase (ChAT) activity assayed 2-6 days post-stress. This NT + BMP combination preserved ChAT activity better than either NTs or BMPs alone, and was effective even if trophic factor addition was delayed until 12 h after stress onset. A general caspase inhibitor (qVD-OPH, 10 μg/mL) also increased survival of stressed cholinergic neurons, but its protection of ChAT activity was shorter lived than that produced by the NT + BMP combination. Neither the NT + BMP combination nor the caspase inhibitor reduced the OA-induced increase in tau phosphorylation. These findings indicate that NTs and BMPs have synergistic protective effects against an OA stress, and suggest that at least some of these protective effects occur upstream of caspase activation.",
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