VGF EXPRESSION IN THE BRAIN

VGF is a neuronal polypeptide first identified as a cDNA clone in a ge ne library from nerve growth factor-stimulated PC12 cells. In the pres ent paper, the expression of VGF is examined for the first time throug hout the adult rat central nervous system with immunocytochemistry and Northern blot analysis. VGF RNA was found in all brain regions studie d, including hypothalamus, hippocampus, cerebellum, olfactory bulb, an d cortex. In contrast to the relatively strong immunostaining of hypot halamic neurons, the level of VGF RNA expression in the hypothalamus w as relatively low in comparison with other brain regions. With the aid of antisera raised against bacterially produced recombinant proteins containing parts of the VGF sequence, immunoreactive neurons were dete cted throughout the brain, including regions of the olfactory tubercle , caudate-putamen, thalamus, cortex, amygdala, hypothalamus, midbrain, and hippocampus. VGF-immunoreactive neurons did not contain detectabl e amounts of nerve growth factor receptor; other neurons that showed n erve growth factor receptor immunoreactivity expressed no VGF immunore activity. The lack of colocalization of VGF and nerve growth factor re ceptor suggests that, unlike expression in PC12 cells, VGF expression in neurons from the central nervous system does not require nerve grow th factor stimulation. Within the hippocampus, the location of VGF-imm unoreactive cells was suggestive of inhibitory interneurons. VGF-immun oreactive axons and terminals were found throughout the brain. These o bservations extend our earlier work on VGF expression in the hypothala mus to other regions of the brain and support the conclusion that alth ough VGF expression is only detected in subsets of neurons in each bra in region, these subsets are widely distributed throughout the central nervous system. (C) 1994 Wiley-Liss, Inc.