title: Trophic factor and hormonal regulation of neurite outgrowth in sensory neuron-like 50B11 cells.
abstract: Sensory axon integrity and regenerative capacity are important considerations in understanding neuropathological conditions characterized by hyper- or insensitivity. However, our knowledge of mechanisms regulating axon outgrowth are limited by an absence of suitable high-throughput assay systems. The 50B11 cell line generated from rat embryonic dorsal root ganglion neurons offers a promising model for screening assays. Prior characterization shows that these cells express cytoskeletal proteins and genes encoding ion channels and neurotrophin receptors in common with sensory nociceptor neurons. In the present study we further characterized 50B11 cells in regard to their phenotypes and responsiveness to neurotrophic and hormonal factors. 50B11 cells express neuronal cytoplasmic proteins including beta-3 tubulin, peripherin (a marker of unmyelinated neurons), and the pan-neuronal ubiquitin hydrolase, PGP9.5. Only PGP9.5 immunoreactivity was uniformly distributed throughout soma and axons, and therefore presents the best means for visualizing the entire axon arbor. All cells co-express both NGF and GDNF receptors and addition of ligands increased neurite length. 50B11 cells also showed immunoreactivity for the estrogen receptor-α and the angiotensin receptor type II, and both 17-β estradiol and angiotensin II increased outgrowth by differentiated cells. 50B11 cells therefore show features reported previously for primary unmyelinated nociceptor neurons, including responsiveness to classical neurotrophins and hormonal modulators. Coupled with their ease of culture and predictable differentiation, 50B11 cells represent a promising cell line on which to base assays that more clearly reveal mechanisms regulating axon outgrowth and integrity.
authors.affiliation: Institute for Neurological Discoveries, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Aritra
authors.initials: A
authors.lastname: Bhattacherjee
authors.affiliation: Institute for Neurological Discoveries, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Institute for Neurological Discoveries, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: psmith@kumc.edu.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Smith
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D004967:Estrogens; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006728:Hormones; D009414:Nerve Growth Factors; D000804:Angiotensin II; D004958:Estradiol; D020932:Nerve Growth Factor
keywords: ANGII; AT2; Axon; DRG; Dorsal root ganglion; E2; ER; GDNF; High throughput screening; Hormones; NGF; Neurotrophic factors; Outgrowth; PGP9.5; angiotensin II; angiotensin II receptor type 2; dorsal root ganglion; estradiol or estrogen; estrogen receptor; glial cell line derived neurotrophic factor; immunoreactivity; ir; nerve growth factor; protein gene product 9.5