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First published online September 22, 2005
doi: 10.1242/10.1242/jcs.02572

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Activation of protein kinase CßI constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons

¹ Research Centre for Cellular and Molecular Neurobiology, Developmental Neurobiology Unit, University of Liège, Av. de l'Hopital 1 (B36), 4000 Liège, Belgium
² Department of Neurology, University of Liège, Av. de l'Hopital 13 (B35), Sart-Tilman, 4000 Liège, Belgium
³ Department of Otorhinolaryngology, University of Liège, Av. de l'Hopital 13 (B35), Sart-Tilman, 4000 Liège, Belgium

^* Author for correspondence (e-mail: flallemend{at}student.ulg.ac.be)

Accepted 6 July 2005

In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this condition have not presented complete effectiveness in protecting the integrity of cochlear neural elements. In this context, the protein kinase C (PKC) family of enzymes are important signalling molecules that play a role in preventing neurodegeneration after nervous system injury. The present study demonstrates, for the first time, that the PKC signalling pathway is directly neurotrophic to axotomised spiral ganglion neurons (SGNs). We found that PKCßI was strictly expressed by postnatal and adult SGNs both in situ and in vitro. In cultures of SGNs, we observed that activators of PKC, such as phorbol esters and bryostatin 1, induced neuronal survival and neurite regrowth in a manner dependent on the activation of PKCßI. The neuroprotective effects of PKC activators were suppressed by pre-treatment with LY294002 (a PI3K inhibitor) and with U0126 (a MEK inhibitor), indicating that PKC activators promote the survival and neurite outgrowth of SGNs by both PI3K/Akt and MEK/ERK-dependent mechanisms. In addition, whereas combining the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) was shown to provide only an additive effect on SGN survival, the interaction between PKC and neurotrophin signalling gave rise to a synergistic increase in SGN survival. Taken together, the data indicate that PKCßI activation represents a key factor for the protection of the integrity of neural elements in the cochlea.

Key words: Cochlea, Peripheral nervous system, PKC, Neuroprotection, Signal transduction, Neuritogenesis

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