Overexpression of brain-derived neurotrophic factor enhances sensory innervation and selectively increases neuron number

Target-derived neurotrophin growth factors have significant effects on the development and maintenance of the mammalian somatosensory system. Studies of transgenic mice that overexpress neurotrophins NGF and neurotrophin 3 (N T-3) at high levels in skin have shown increased sensory neuron number and enhanced innervation of specific sensory ending types. The effects of two o ther members of this family, BDNF and NT-4, on sensory neuron development a re less clear. This study examined the role of brain-derived neurotrophic f actor (BDNF) using transgenic mice that overexpress BDNF in epithelial targ et tissues of sensory neurons. BDNF transgenic mice had an increase in peri pheral innervation density and showed selective effects on neuron survival. Neuron number in trigeminal ganglia, DRG, and SCG were unchanged, although a 38% increase in neurons comprising the placode-derived nodose-petrosal c omplex occurred. BDNF transgenic skin showed notable enhancement of innerva tion to hair follicles as detected by PGP9.5 immunolabeling. In nonhairy pl antar skin, Meissner corpuscle sensory endings were larger, and the number of Merkel cells with associated innervation was increased. In trigeminal ga nglia, neurons expressing trkB receptor were increased threefold, whereas t rkA-positive neurons doubled. Analysis of trkB by Northern, reverse transcr iption-PCR, and Western assays indicated a modest increase in the expressio n of the T1 truncated receptor and preferential distribution to the periphe ry. These data indicate that skin-derived BDNF does not enhance survival of cutaneous sensory neurons, although it does promote neurite innervation of specific sites and sensory end organs of the skin.