Background: Vagus nerve stimulation (VNS) is used to treat pharmacotherapy-resistant epilepsy and depression. The mechanisms underlying the therapeutic efficacy of VNS remain unclear and have not yet been elucidated. We previously showed that VNS triggers neurochemical and molecular changes in the rat brain. We here examined the effects of VNS on rat hippocampal neuronal plasticity and behavior. Methods: Cell proliferation in the hippocampus of rats subjected to acute or chronic 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. Chronic VNS treated animals were subjected to forced swim or elevated plus-maze tests. Results: Acute VNS induced a rapid and long lasting increase in the number of BrdU+ cells in the dentate gyrus as well as an increase in the amount of DCX immunoreactivity and in the number of DCX+ neurons. Chronic VNS induced long-lasting increases in the amount of BDNF 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 behavior of rats in the forced swim or elevated plus-maze tests. Conclusion: 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 behavioral alterations characteristic of an antidepressant or anxiolytic action.

VAGUS NERVE STIMULATION INDUCES NEURONAL PLASTICITY IN THE RAT HIPPOCAMPUS

FOLLESA, PAOLO
2010-01-01

Abstract

Background: Vagus nerve stimulation (VNS) is used to treat pharmacotherapy-resistant epilepsy and depression. The mechanisms underlying the therapeutic efficacy of VNS remain unclear and have not yet been elucidated. We previously showed that VNS triggers neurochemical and molecular changes in the rat brain. We here examined the effects of VNS on rat hippocampal neuronal plasticity and behavior. Methods: Cell proliferation in the hippocampus of rats subjected to acute or chronic 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. Chronic VNS treated animals were subjected to forced swim or elevated plus-maze tests. Results: Acute VNS induced a rapid and long lasting increase in the number of BrdU+ cells in the dentate gyrus as well as an increase in the amount of DCX immunoreactivity and in the number of DCX+ neurons. Chronic VNS induced long-lasting increases in the amount of BDNF 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 behavior of rats in the forced swim or elevated plus-maze tests. Conclusion: 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 behavioral alterations characteristic of an antidepressant or anxiolytic action.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/30839
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