In utero gene transfer reveals survival effects of nerve growth factor on rat brain cholinergic neurones during development

Authors

  • Alberto Martínez-Serrano,

    1. Department of Physiology and Neuroscience, Wallenberg Neuroscience Center, Section of Neurobiology, University of Lund, Sölvegatan 17, S-223 62-Lund, Sweden, Center of Molecular Biology ‘Severo Ochoa’, Autonomous University of Madrid-CSIC, Campus Cantoblanco, 28049-Madrid, Spain
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  • Martin Olsson,

    1. Department of Physiology and Neuroscience, Wallenberg Neuroscience Center, Section of Neurobiology, University of Lund, Sölvegatan 17, S-223 62-Lund, Sweden, Center of Molecular Biology ‘Severo Ochoa’, Autonomous University of Madrid-CSIC, Campus Cantoblanco, 28049-Madrid, Spain
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  • Monte A. Gates,

    1. Department of Physiology and Neuroscience, Wallenberg Neuroscience Center, Section of Neurobiology, University of Lund, Sölvegatan 17, S-223 62-Lund, Sweden, Center of Molecular Biology ‘Severo Ochoa’, Autonomous University of Madrid-CSIC, Campus Cantoblanco, 28049-Madrid, Spain
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  • Anders Björklund

    1. Department of Physiology and Neuroscience, Wallenberg Neuroscience Center, Section of Neurobiology, University of Lund, Sölvegatan 17, S-223 62-Lund, Sweden, Center of Molecular Biology ‘Severo Ochoa’, Autonomous University of Madrid-CSIC, Campus Cantoblanco, 28049-Madrid, Spain
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Abstract

Nerve growth factor (NGF) is a maintenance factor for cholinergic neurones in the brain, but its properties as a developmental survival factor are largely unknown. The low accessibility of the developing mammalian brain to experimental manipulation makes it difficult to increase NGF levels during the early phases of brain development. In the present study we have used an in utero, ex-vivo gene transfer approach to explore NGF actions during development of the cholinergic system in the rat brain. Significantly increased numbers of cholinergic neurones were found only in the mesopontine complex in animals receiving NGF-secreting transplants, whereas the cholinergic neurones in the basal forebrain and striatum were not clearly affected. The present results suggest that overexpression of NGF during development may promote the survival of distinct populations of central cholinergic neurones into adulthood.

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