Neuronal Metabolic Basis of the Conditioning Lesion Effect

Abstract

The cell body response to axonal interruption is a fundamental reaction of the neuron. This activates the “growth mode” of neuronal metabolism, a genomic induction that leads to the accelerated turnover of messenger ribonucleic acid (mRNA) in association with the production of new messenger RNA and additional nucleolar DNA (Torvik and Skjorten 1974; Watson 1974; Grafstein and McQuarrie 1978; Hoffman et al. 1987). The “growth mode” gives first priority to the synthesis and axonal transport of structural and regulatory proteins that are used to assemble microtubules and microfilaments: tubulin, actin, microtubule associated proteins (MAPs), and calmodulin (Grafstein and McQuarrie 1978; McQuarrie 1983, 1988; Tetzlaff et al. 1986; Hoffman et al. 1987). Increases in transport are also seen for a trace protein, GAP-43, that appears to catalyze membrane assembly (Skene and Willard 1981 a; Jacobson et al. 1986; Perry et al. 1987). There is a concurrent reduction in metabolic activities that support the production of neurotransmitter molecules and neurofilaments (Grafstein and McQuarrie 1978; Hoffman and Lasek 1980; Tetzlaff et al. 1986; Hoffman et al. 1987; Wong and Oblinger 1987). The reduction in neurofilament transport causes a thinning of parent axons; radial regrowth does not occur until reconnection of the daughter axon with a functionally matched target organ (Cragg and Thomas 1961; Zalewski 1970; Hoffman et al. 1985, 1987; Wong and Oblinger 1987).