The International Journal of Neuropsychopharmacology

Table of Contents - 2009 - Volume 12, Issue 09  

Research Article

Chronic vagus nerve stimulation induces neuronal plasticity in the rat hippocampus

Francesca Biggioa1a2, Giorgio Gorinia1, Cinzia Utzeria1, Pierluigi Ollaa1, Francesco Marrosua3, Italo Mocchettia2 and Paolo Follesaa1 c1

a1 Department of Experimental Biology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Cagliari, Italy

a2 Department of Neuroscience, Georgetown University, Washington DC, USA

a3 Department of Neurological and Cardiovascular Sciences, University of Cagliari, Cagliari, Italy

Abstract

Vagus nerve stimulation (VNS) is used to treat pharmacotherapy-resistant epilepsy and depression. However, the mechanisms underlying the therapeutic efficacy of VNS remain unclear. We examined the effects of VNS on hippocampal neuronal plasticity and behaviour in rats. Cell proliferation in the hippocampus of rats subjected to acute (3 h) or chronic (1 month) VNS was examined by injection of bromodeoxyuridine (BrdU) and immunohistochemistry. Expression of doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) was evaluated by immunofluorescence staining. The dendritic morphology of DCX+ neurons was measured by Sholl analysis. Our results show that acute VNS induced an increase in the number of BrdU+ cells in the dentate gyrus that was apparent 24 h and 3 wk after treatment. It also induced long-lasting increases in the amount of DCX immunoreactivity and in the number of DCX+ neurons. Neither the number of BrdU+ cells nor the amount of DCX immunoreactivity was increased 3 wk after the cessation of chronic VNS. Chronic VNS induced long-lasting increases in the amount of BDNF immunoreactivity and the number of BDNF+ cells as well as in the dendritic complexity of DCX+ neurons in the hippocampus. In contrast to chronic imipramine treatment, chronic VNS had no effect on the behaviour of rats in the forced swim or elevated plus-maze tests. Both chronic and acute VNS induced persistent changes in hippocampal neurons that may play a key role in the therapeutic efficacy of VNS. However, these changes were not associated with evident behavioural alterations characteristic of an antidepressant or anxiolytic action.

(Received December 02 2008)

(Reviewed January 20 2009)

(Revised January 30 2009)

(Accepted February 09 2009)

(Online publication March 24 2009)

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Correspondence:

c1 Address for correspondence: Dr P. Follesa, Department of Experimental Biology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Cagliari, 09100, Italy. Tel.: +390706754138 Fax: +390706754166 Email: follesa@unica.it

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