title: Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain.
abstract: Vagus nerve stimulation therapy, effective for treatment-resistant epilepsy, has recently been approved also for treatment-resistant depression; nevertheless, the molecular mechanism(s) underlying its therapeutic action remains unclear. Given that neurotrophic factors and monoamines could play a crucial role in the pathophysiology of depression, we tested whether vagus nerve stimulation increases the expression of brain-derived neurotrophic factor, fibroblast growth factor, and nerve growth factor as well as the concentration of norepinephrine in the rat brain. Rats were implanted with a vagus nerve stimulator device and the effects of acute stimulation were evaluated on the growth factors mRNA levels and norepinephrine concentration by ribonuclease protection assay and microdialysis, respectively. We found that acute vagus nerve stimulation increased the expression of brain-derived neurotrophic factor and fibroblast growth factor in the hippocampus and cerebral cortex, decreased the abundance of nerve growth factor mRNA in the hippocampus, and, similar to the antidepressant drug venlafaxine, increased the norepinephrine concentration in the prefrontal cortex. This study demonstrates that acute vagus nerve stimulation triggers neurochemical and molecular changes in the rat brain involving neurotransmitters and growth factors known to play a crucial role in neuronal trophism. These new findings contribute to the elucidation of the molecular mechanisms underlying the therapeutic actions of vagus nerve stimulation in both treatment-resistant depression and epilepsy.
authors.affiliation: Department of Experimental Biology, Section of Neuroscience, University of Cagliari, Cagliari, Italy. follesa@unica.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Follesa
authors.forename: Francesca
authors.initials: F
authors.lastname: Biggio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gorini
authors.forename: Stefania
authors.initials: S
authors.lastname: Caria
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talani
authors.forename: Laura
authors.initials: L
authors.lastname: Dazzi
authors.forename: Monica
authors.initials: M
authors.lastname: Puligheddu
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004558:Electric Stimulation; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000096:biosynthesis*; D023282:Nuclease Protection Assays; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D009638:Norepinephrine