Our lab is interested in understanding how neurotrophic growth factors, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), regulate nervous system development and function. We study neurotrophin action through the identification of gene products that these growth factors regulate in the CNS and PNS, determining how these proteins are involved in neurogenesis, axonal outgrowth and pathfinding, synaptogenesis, and synaptic plasticity, using cellular and molecular tools, and knockout mouse models. Together with the Benson lab, we’re currently examining how the NGF-regulated cell surface adhesion protein, called NILEGP or L1, an immunoglobulin (Ig) superfamily member that is expressed primarily in the nervous system, regulates axonal outgrowth, branching, pathfinding, and fasciculation, as well as neuronal migration. Of note, inherited X-linked mutations in L1 result in hydrocephalus and mental retardation (CRASH and MASA syndromes). In addition, we’re trying to understand how the neurotrophin-inducible gene Vgf, encoding a secreted ‘granin-like’ protein and peptide precursor, controls energy expenditure, memory, and depressive behavior. Recent collaborative studies with the Huntley, Alberini, Shapiro, and Duman laboratories indicate that VGF-derived peptides injected into the brain have anti-depressant efficacy, consistent with abnormalities noted in memory tasks and depressed behavior in VGF knockout mice, and that VGF regulates hippocampal synaptic activity via a BDNF-dependent mechanism. We are developing novel conditional and humanized knockout models to better understand VGF function in the developing and adult hippocampus, hypothalamus, and sympathetic nervous system.
VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism. Lin WJ, Jiang C, Sadahiro M, Bozdagi O, Vulchanova L, Alberini CM, Salton SR. J Neurosci. 2015 Jul 15;35(28):10343-56. doi: 10.1523/JNEUROSCI.0584-15.2015. PMID: 26180209.
Regulated expression and secretion of BDNF, which activates TrkB receptor signaling, is known to play a critical role in cognition. Identification of additional modulators of cognitive behavior that regulate activity-dependent BDNF secretion and/or potentiate TrkB receptor signaling would therefore be of considerable interest.
Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice. Foglesong GD, Huang W, Liu X, Slater AM, Siu J, Yildiz V, Salton SR, Cao L. Endocrinology. 2016 Mar;157(3):983-96. PMID: 26730934
VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism. Lin WJ, Jiang C, Sadahiro M, Bozdagi O, Vulchanova L, Alberini CM, Salton S.R. J. Neurosci. 2015 Jul 15;35(28):10343-56. PMID: 26180209.
Role of VGF-derived carboxy-terminal peptides in energy balance and reproduction: analysis of “humanized” knockin mice expressing full-length or truncated VGF. Sadahiro M, Erickson C, Lin WJ, Shin AC, Razzoli M, Jiang C, Fargali S, Gurney A, Kelley KA, Buettner C, Bartolomucci A, Salton SR. Endocrinology. 2015 May;156(5):1724-38. doi: 10.1210/en.2014-1826. Epub 2015 Feb 12. PMID: 25675362.
Fairbanks, C.A., Peterson, C.D., Speltz, R.H., Riedl, M.S., Kitto, K.F., Dykstra, J.A., Braun, P.D., Sadahiro, M., Salton, S.R., Vulchanova, L. (2014). The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury induced hypersensitivity. Pain 155(7):1229-1237.
Fargali, S., Garcia, A., Sadahiro, M., Jiang, C., Janssen, W.G., Lin, W.J., Cogliani, V., Elste, A., Mortillo, S., Cero, C., Veitenheimer, B., Graiani, G., Pasinetti, G.M., Mahata, S.K., Osborn, J.W., Huntley, G.W., Phillips, G.R., Benson, D.L., Bartolomucci, A., Salton, S.R. (2014). The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure. FASEB J 28(5):2120-2133.
Jiang, C. and Salton, S.R. (2013). The role of neurotrophins in major depressive disorder. Transl. Neurosci. 4:46-58.
Lin, W.J. and Salton, S.R. (2013). The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms. Front. Endocrinol. 4:96.
Boersma, G.J., Salton, S.R., Spritzer, P.M., Steele, C., Carbone, D.L. (2012). Models and mechanisms of metabolic regulation: Genes, stress and the HPA and HPG axes. Horm. Metab. Res. 44:598-606.
Fargali, S., Sadahiro, M., Jiang, C., Frick, A.L., Indall, T., Cogliani, V., Welagen, J., Lin, W.J., Salton, S.R. (2012). Role of neurotrophins in the development and function of neural circuits that regulate energy homeostasis. J. Mol. Neurosci. 48:654-659.
Fargali, S., Scherer, T., Shin, A.C., Sadahiro, M., Buettner, C., Salton, S.R. (2012). Germline ablation of VGF increases lipolysis in white adipose tissue. J. Endocrinol. 215:313-322.