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P a r t i c i p a n t s :
Maria Egle De Stefano, professor; Arianna Del Signore,
Lucia Leone, Loredana Lombardi, post-doc fellows.
C o l l a b o r a t i o n s :
Istituto Superiore di Sanità, Laboratorio di Biologia Cellulare,
Roma (Dr. Tamara Petrucci); Centro di Farmacologia Cellulare e
Molecolare, CNR, Dipartimento di Farmacologia Medica,
Università di Milano (Dr. Cecilia Gotti); Dipartimento di
Genetica e Biologia Molecolare, Sapienza-Università di Roma
(Prof. Ernesto Di Mauro, Prof. Alberto Oliverio);
Dipartimento di Scienze Biologiche, Università di Napoli “Federico
II” (Prof. Carla Perrone Capano).
Report of activity
Aim of this project is the characterisation in
rodent superior cervical ganglion (SCG) of the
molecular mechanisms and structural changes
involved in the establishment, maintenance and
plasticity of the reciprocal interactions between
pre- and post-ganglionic neurones and between
post-ganglionic neurones and their target organs.
Damage of the ganglionic connectivities, consequent
to pre- and post-ganglionic nerve crush, or
to the lack of dystrophin, will be used as a tool to
perform our investigation.
Specifically, we focused on: (i) the possible involvement
of the plasminogen enzymatic cascade in the
remodelling of the rat SCG intraganglionic synapses
induced by pre- and post-ganglionic nerve crush;
(ii) the role of dystrophin and SCG target organs in
the maintenance of the structural and functional
integrity of ganglionic circuits in mice.
(i) Axotomy of SCG neurons is characterized by
peripheral regeneration of injured axons and temporary
disassembly of the intraganglionic synapses,
necessary for synaptic silencing. Both events require
remodelling of the extracellular matrix achieved
through controlled proteolysis of its components by
89
Molecular recognition in biomolecules - AREA 4
Neuronal response to experimental interruption
of the neural circuit: a molecular and structural study
in autonomic ganglia in vivo
Principal investigator: Paola Paggi
Professor of Physiology
Dipartimento di Biologia Cellulare e dello Sviluppo
Tel: (+39) 06 49912323; Fax: (+39) 06 49912351
paola.paggi@uniroma1.it
different enzymatic systems. Therefore, we investigated
the involvement of the plasminogen enzymatic
cascade in response to axotomy of rat SCG neurons.
All the components of this enzymatic pathway:
tissue plasminogen activator (tPA), plasminogen and
their membrane receptor annexin II, as well tPA
inhibitor-1 (PAI-1), are constitutively expressed in
uninjured SCGs and increase significantly after SCG
neuron axotomy. Immunolocalization of plasminogen,
the key protein converted into the enzymatically
active plasmin by tPA in both neuronal and nonneuronal
cells, indicate a contribution by all cell
types (Fig. 1). The time course of activation of
tPA/plasmin enzymatic pathway suggests its
involvement in both axonal regeneration and intraganglionic
synapse remodelling (De Stefano et al.,
2007).
(ii) We previously reported that in the SCG of dystrophic
mdx mice, which lack full-length dystrophin,
there is a loss of neurons projecting to SCG muscular
targets, like the iris. Nonetheless, surviving neurons,
innervating either iris or submandibular gland
(SuGl), a SCG non-muscular target, underwent
reduced axon defasciculation and terminal branching.
Analysis of the components of the NGF signaling
complex, during early post-natal development,
revealed that levels of pro-apoptotic proNGF in mdx
mouse iris, but not in the SuGl, are higher than in the
wild-type. This increase, along with reduced levels of
NGF receptors (TrkA and p75NTR) in SCG, may be
partly responsible for the observed loss of neurons
projecting to the iris. These alterations, combined
with a reduction in polysialylated-NCAM and neurofilament
protein levels in SCG, may also account for
reduced axon defasciculation and terminal branching
in mdx mouse SCG targets (Lombardi et al., 2008.).
Selected publications
De Stefano ME, Leone L, Moriconi C, Del
Signore A, Petrucci TC, Paggi P. Involvement of