Journal of Molecular Neuroscience

, Volume 27, Issue 1, pp 65–77

Metabolic activity

A novel indicator of neuronal survival in the murine dopaminergic cell line CAD
  • Gonzalo Arboleda
  • Catherine Waters
  • Rosemary M. Gibson
Original Article

Abstract

Apoptosis is implicated in many neurodegenerative diseases, including Parkinson’s disease (PD). Neuroprotective strategies targeting apoptosis need to preserve functional integrity of the saved cells to be effective. The aim of the present study was to evaluate a novel approach for analyzing neuronal function that monitors cellular metabolic responses to receptor activation using the microphysiometer. N-Acetyl-sphingosine (C2-ceramide) induced cell death of the neuronal cell line, Cath.a-differentiated (CAD) cells, which resemble catecholaminergic cells of the CNS, and provide a useful in vitro model for the cells affected in PD. C2-ceramide also suppressed the metabolic response of CAD cells to muscarinic receptor activation. Pretreatment with the caspase inhibitor Boc-Asp-(OMe)-fluoromethylketone (BAF) plus neurotrophin-3 (NT-3) reduced C2-ceramide-induced CAD cell death, delaying cell death more effectively than either agent alone; and, most significantly, BAF and NT-3 enabled the cells remaining 24 h after toxin treatment to generate a normal metabolic response to the muscarinic agonist carbachol. On the basis of these results, we suggest that measuring metabolic responses to receptor activation is a useful method for following neuronal viability after toxin treatment and that the combination of caspase inhibitors and neurotrophic factors might be a plausible strategy for improving neuronal survival, with critical preservation of metabolic function.

Index Entries

Neuronal apoptosis ceramide catecholaminergic cells CAD caspase inhibitor neurotrophin-3 microphysiometer metabolic activity 

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Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  • Gonzalo Arboleda
    • 1
  • Catherine Waters
    • 1
  • Rosemary M. Gibson
    • 1
  1. 1.Faculty of Life SciencesUniversity of ManchesterManchesterUK
  2. 2.Departamento de Ciencias Básicas, Facultad de MedicinaUniversidad del RosarioBogotáColombia

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