title: Chronic vagus nerve stimulation induces neuronal plasticity in the rat hippocampus.
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.
authors.affiliation: Department of Experimental Biology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, Cagliari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Biggio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gorini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Utzeri
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Olla
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.forename: Italo
authors.initials: I
authors.lastname: Mocchetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Follesa
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D049109:Cell Proliferation; D003712:Dendrites / Q000502:physiology; D018891:Dentate Gyrus / Q000502:physiology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004599:Electric Stimulation Therapy; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D007099:Imipramine