Expression of themRNA encoding VGF, a neural-specific peptide precursor, in the developing and adult rat central nervous systems, and its modulation in response to changes in neuronal electrical activity, seizure, and lesion

VGF is the non-acronymous name of a peptide precursor expressed by neurons and neuroendocrine cells, whose transcription and secretion are rapidly induced by neurotrophins and by depolarization. To gain insight into the possible functions and regulation of VGF in vivo, this study characterizes the distribution of VGF mRNA in the developing and mature rat central nervous system, compares it to the distributions of mRNAs encoding the Trk neurotrophin receptors, and describes its modulation in response to perturbation of neuronal electrical activity, seizure, and lesion.;VGF expression was first detectable at embryonic day 11.5 in the primordia of cranial, sympathetic, and dorsal root ganglia, and its distribution expanded throughout development to include significant expression throughout the brain and spinal cord of the adult rat. VGF mRNA levels are particularly high during critical developmental periods in many regions of the nervous system. Significant overlap between VGF and various trk mRNAs was observed, and though no trk mRNA exclusively colocalized with VGF message, good correlation was found between the distributions of the VGF and trkB kinase mRNAs, implying that activation of TrkB may account for much VGF expression.;Furthermore, we have shown that VGF mRNA is regulated in the CNS by manipulations affecting neuronal activity and by lesion. Inhibition of retinal electrical activity during the visual critical period rapidly repressed VGF mRNA in the lateral geniculate. In the adult, kainate-induced seizures up-regulated VGF in dentate granule cells, hippocampal pyramidal cells, and cortex within hours. Direct cortical lesion produced rapid, complex changes in VGF expression, including strong induction in ipsilateral cortex, and deep repression in the deafferented ipsilateral striatum. Days later, following normalization of cortical VGF expression, we observed delayed induction of VGF mRNA in a striatal region where compensatory cortical sprouting occurs. Taken together these observations strongly suggest that in addition to a likely role in the mediation of neurotrophin effects, VGF or the peptides derived from it may also play a critical role in the synaptogenesis and synaptic reorganization which often result from changing afferent input during development and in the adult, in both physiological and pathological conditions.