Aldo Rustioni, M.D.

rustioni@med.unc.edu

Lab Personnel

Professor

• M.D., Parma, 1965
• Joined the Department in 1973

Funding Sources

• National Institutes of Health

Research Interests

My laboratory is focused on two main projects at the moment.

One stems from the discovery, in Dr. Otey's lab, of a new intracellular protein associated with the actin cytoskeleton and cell adhesion in fibroblasts. This protein, called palladin, has been shown to play a critical role in the assembly and maintainance of cell shape. Palladin is ubiquitous in embryonic mice but dramatically downregulated in most adult tissues. An isoform of palladin (n-palladin), however, is still present in the brain and spinal cord. Since we determined that high levels of n-palladin are expressed in excitatory synapses in the adult nervous system, it is apparent that n-palladin belongs to an ever growing group of proteins in the cytomatrix of the synapse. The search is now open for the functional attributes of n-palladin and, for this purpose, a concerted effort is developed by Rustioni's and Otey's labs to perform experiments at the molecular, cellular and whole system level. Techniques including immunoblots, microinjections, gene knock-outs and nerve lesions will be used to explore the function of n-palladin in establishing and maintaining the synapse, and in modulating its plasticity in response to injury or repetitive stimulation.

The second main project deals with the role of glutamate receptors in synaptic transmission in the superficial laminae of the dorsal horn of the spinal cord. A considerable amount of work has been already performed to identify, by postembedding immunogold and confocal microscopy, which subunits of both ionotropic and metabotropic receptors are mediating synaptic activity from functionally different primary afferents. Special emphasis at the moment is on determining what subunits might be present also presynaptically and to investigate, on the basis of their distribution, what their role may be in synaptic transmission in superficial laminae, and especially in the mediation of nociception.

Considerable interest is also on receptors for neurokinins (NK) and, in particular, their coexpression and colocalization with glutamate receptors in neurons of superficial laminae of the dorsal horn. Most NK1 receptors that are colocalized with glutamate receptor subunits are colocalized with NMDAR1. With confocal microscopy, we are exploring now the hypotheses that alterations in synaptic input may induce upregulation of coexpression and colocalization of the two receptors and that this might contribute to hyperalgesia in response to peripheral nerve injury.

Selected Publications

• Lucifora S, Willcockson HH, Lu CR, Darstein M, Phend KD, Valtschanoff JG, Rustioni A. (2006) Presynaptic low- and high-affinity kainate receptors in nociceptive spinal afferents. Pain. Jan 120(1-2):97-105.
• Rustioni A. (2005) Modulation of sensory input to the spinal cord by presynaptic ionotropic glutamate receptors. Archives Italiennes de Biologie. 143:103-112.
• Lu CR, Willcockson HH, Phend KD, Lucifora S, Darstein M, Valtschanoff JG, and Rustioni A. (2005) Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn. J. Comp. Neurol. Apr. 20;486(2):169-178.
• Hwang SJ, Burette A, Rustioni A, Valtschanoff JG. (2004) Vanilloid receptor VR1-positive primary afferents are glutamatergic and contact spinal neurons that co-express neurokinin receptor NK1 and glutamate receptors. J. Neurocytol. May;33(3):321-9.
• Boukhelifa M., Hwang S.J., Valtschanoff J.G., Meeker R.B., Rustioni A., Otey C.A . (2003) A critical role for palladin in astrocyte morphology and response to injury. Molec. Cell. Neurosci. Aug;23(4):661-8.
• Lu C.R., Hwang S.J., Phend K.D., Rustioni A., Valtschanoff J.G. (2003) Primary afferent terminals that express presynaptic NR1 in rats are mainly from myelinated, mechanosensitive fibers. J. Comp. Neurol. 460: 191-202.
• Lu C.R., Hwang S.J., Phend K.D., Rustioni A., Valtschanoff J.G. (2002) Primary afferent terminals in spinal cord express presynaptic AMPA receptors. J. Neurosci. 22: 9522-9529.
• Hwang S.J., Rustioni A., Valtschanoff J.G. (2001) Kainate receptors in primary afferents to the rat gracile nucleus. Neurosci. Lett. 312: 137-140.
• Valtschanoff J.G., Rustioni A., Guo A. and Hwang S.J. (2001) Vanilloid receptor VR1 is both pre- and postsynaptic in the superficial laminae of the rat dorsal horn. J. Comp. Neurol. 436: 225-235.
• Hwang S.J., Pagliardini S., Boukhelifa M., Parast, M.M., Otey C.A., Rustioni A., and Valtschanoff J.G. (2001) Palladin is expressed preferentially in excitatory terminals in the rat central nervous system. J. Comp. Neurol. 436: 211-224.
• Hwang S.J., Pagliardini S., Rustioni A. and Valtschanoff J.G. (2001) Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord. J. Comp. Neurol. 436: 275-289.