Peripheral Mechanisms and Injury

The team is investigating plasticity of urogenital autonomic nerves and pain pathways. Our two main aims are:
(1) To identify the role of neurotrophic factors and endogenous steroids in the development, plasticity and regenerative processes of urogenital nerves.
(2) To develop strategies for prevention or reversal of structural and functional remodelling in spinal cord circuits after injury, specifically to improve regulation of urogenital organs and attenuation of pain.

We address these aims using an array of techniques, including neuroanatomical methods (tract tracing, nerve lesions), immunofluorescence and microscopy, primary neuronal cultures of adult sensory and autonomic neurons, knockout mice, molecular analyses of signalling cascades, physiological assessment of neuronal function using organ bath studies or electrophysiology. Examples of current projects are:

Examples of current projects

• Structural changes in sensory and spinal pathways after spinal cord injury, especially focusing on changes relevant to urogenital dysfunction and pain
• The GDNF family of ligands and their role in development, plasticity and regeneration of urogenital autonomic nerves
• Signalling mechanisms of androgens and estrogens in peripheral sensory and autonomic neurons, including their effects during inflammation and disease (eg diabetic neuropathy).
• Plasticity of bladder afferent and efferent pathways, especially under inflammatory or pain conditions.
• Roles of androgens and estrogens in establishing sexual dimorphism in urogenital autonomic nerves

Group Leader

A/Prof. Janet Keast

Staff

• Dr Morven Cameron, PhD, Postdoctoral Fellow
• Dr Matthew Nangle, PhD, Postdoctoral Fellow
• Dr Mitchell Quinlivan, PhD, Postdoctoral Fellow
• Ms Adrianna Kalous, BMedSc(Hons), PhD student
• Ms Mehreen Arshi, BMedSci, Research Assistant
• Ms Angela O'Connor, BSc, Hons student

Publications

Yan H, Keast JR (2008) Neurturin regulates postnatal differentiation of parasympathetic pelvic ganglion neurons, initial axonal projections, and maintenance of terminal fields in male urogenital organs. J Comp Neurol, 507(2), 1169-83.

Forrest SL, Keast JR (2008) Expression of receptors for glial cell line-derived neurotrophic factor family ligands in sacral spinal cord reveals separate targets of pelvic afferent fibers. J Comp Neurol, 506(6), 989-1002.

Purves-Tyson TD, Arshi MS, Handelsman DJ, Cheng Y, Keast JR (2007) Androgen and estrogen receptor-mediated mechanisms of testosterone action in male rat pelvic autonomic ganglia. Neuroscience, 148(1), 92-104.

Nangle MR, Keast JR (2007) Reduced efficacy of nitrergic neurotransmission exacerbates erectile dysfunction after penile nerve injury despite axonal regeneration. Exp Neurol, 207(1), 30-41.

Kalous A, Osborne PB, Keast JR (2007) Acute and chronic changes in dorsal horn innervation by primary afferents and descending supraspinal pathways after spinal cord injury. J Comp Neurol, 504(3), 238-53.

Brock JA, Handelsman, DJ, Keast, JR (2007) Postnatal androgen deprivation dissociates the development of smooth muscle innervation from functional neurotransmission in mouse vas deferens. J Physiol, 581, 665-78.

Wanigasekara Y, Keast J (2006) Nerve growth factor, glial cell line-derived neurotrophic factor and neurturin prevent semaphorin 3A-mediated growth cone collapse in adult sensory neurons. Neuroscience, 142(2), 369-379.

Palma CA, Keast JR (2006) Structural effects and potential changes in growth factor signalling in penis-projecting autonomic neurons after axotomy. BMC Neuroscience, 7, 41-53.

Nangle MR, Keast JR (2006) Loss of nitrergic transmission to mouse cavernosum in the absence of neurturin is accompanied by increased response to acetylcholine. British Journal of Pharmacology, 148(4), 423-433.

Llewellyn-Smith IJ, Weaver LC, Keast JR (2006) Effects of spinal cord injury on synaptic inputs to sympathetic preganglionic neurons. Prog Brain Res, 152, 11-26.

Keast JR (2006) Plasticity of pelvic autonomic ganglia and urogenital innervation. Int Rev Cytol., 248, 141-208.

Wanigasekara Y, Keast JR (2005) Neurturin has multiple neurotrophic effects on adult rat sacral parasympathetic ganglion neurons. Eur J Neurosci, 22(3), 595-604.

Purves-Tyson TD, Arshi MS, Keast JR (2005) Pelvic autonomic ganglion neurons of adult male rats are both androgen- and estrogen-sensitive. Auton. Neurosci., 119, 141.

Osborne PB, Halliday GM, Cooper HM, Keast JR (2005) Localization of immunoreactivity for deleted in colorectal cancer (DCC), the receptor for the guidance factor netrin-1, in ventral tier dopamine projection pathways in adult rodents. Neuroscience, 131(3), 671-81.

Nangle MR, Keast, JR (2005) Nitrergic dysfunction in corpus cavernosum from adult mice lacking neurturin or GFR. Auton. Neurosci, 119, 140.

Llewellyn-Smith IJ, Fenwick IM, Collins HL, DiCarlo SE, Keast JR (2005) Intraspinal galanin axons target sympathetic preganglionic neurons regulating the pelvic viscera. Auton. Neurosci., 119, 140.

Llewellyn-Smith IJ, Dicarlo SE, Collins HL, Keast JR (2005) Enkephalin-immunoreactive interneurons extensively innervate sympathetic preganglionic neurons regulating the pelvic viscera. J Comp Neurol, 488(3), 278-89.

Wanigasekara Y, Airaksinen MS, Heuckeroth RO, Milbrandt J, Keast JR (2004) Neurturin signalling via GFRa2 is essential for innervation of glandular but not muscle targets of sacral parasympathetic ganglion neurons. Mol Cell Neurosci, 25(2), 288-300.

Purves-Tyson TD, Keast JR (2004) Rapid actions of estradiol on cyclic AMP response-element binding protein phosphorylation in dorsal root ganglion neurons. Neuroscience, 129(3), 629-627.

Middleton JM, Keast JR (2004) Artifical autonomic reflexes: using functional electrical stimulation to mimic bladder reflexes after injury or disease. Auton Neurosci, 113(1-2), 3-15.

Keast JR (2004) Remodelling of connections in pelvic ganglia after hypogastric nerve crush. Neuroscience, 126(2), 405-414.

Wanigasekara Y, Kepper ME, Keast JR (2003) Immunohistochemical characterisation of pelvic autonomic ganglia in male mice. Cell Tissue Res, 311(2), 175-85.

Purves-Tyson T, Keast JR (2003) Mechanisms of estrogen and neurotrophin signaling in dorsal root ganglion (sensory) and pelvic ganglion (autonomic) neurons. Autonomic Neuroscience: Basic and Clinical 2003.

Kanjhan R, Osborne PB, Ouyang M, Keast JR (2003) Postnatal maturational changes in rat pelvic autonomic ganglion cells: a mixture of steroid-dependent and -independent effects. J Neurophysiol, 89, 315-23.

Bennett HL, Gustafsson JA, Keast JR (2003) Estrogen receptor expression in lumbosacral dorsal root ganglion cells innervating the female rat urinary bladder. Auton Neurosci, 105(2), 90-100.

Keast JR, Gleeson RJ, Shulkes A, Morris MJ (2002) Maturational and maintenance effects of testosterone on terminal axon density and neuropeptide expression in the rat vas deferens. Neuroscience, 112, 391-398.

Meusburger SM, Keast JR (2001) Testosterone and nerve growth factor have distinct but interacting effects on structure and neurotransmitter expression of adult pelvic ganglion cells in vitro. Neuroscience, 108(2), 331-340.

Keast JR, Kepper ME (2001) Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighbours. Eur J Neurosci, 13(2), 211-220.

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