Differential expression of nerve growth factor transcripts in glia and neurons and their regulation by transforming growth factor-beta1

Abstract

Nerve growth factor (NGF) influences neuronal development, function, and response to injury. Using reverse transcriptase polymerase chain reaction, we find that mouse and rat cortex and spinal cord, and both neurons and glia in culture, express NGF mRNA. In the mouse, NGF is regulated by at least two promoters that govern synthesis of four different transcripts, A through D, that are all expressed in the mouse tissues and cells examined. In contrast, rat NGF expression varies with tissue and with cell type: transcript C is expressed strongly in brain but weakly in spinal cord, and transcript D is undetectable in rat central nervous system (CNS). In addition to species- and tissue-specific expression, NGF transcripts also exhibit cell type-specific expression: transcripts B, C and D are expressed in rat astrocytes but poorly or not at all in rat neurons, identifying glia as an important source of NGF in rat. NGF increases sharply after injury. TGF-beta1, which also increases immediately after injury, induces NGF mRNA and protein in rat and mouse glia but not in neurons. Furthermore, transcripts A, B and D, but not C, are upregulated by TGF-beta1 in mouse glia, whereas in rat glia, the major responsive transcript is C. Thus, there may be multiple TGF-beta1-responsive elements in the NGF promoters located upstream of exons 1 and 3 that may differ between mouse and rat. Moreover, NGF transcripts are differentially expressed in a species-, cell type-, and inducer-specific manner. These results have implications for the use of mice versus rats as models for the study of NGF regulation following CNS injury.