1,721,066 research outputs found
VAGUS NERVE STIMULATION INDUCES NEURONAL PLASTICITY IN THE RAT HIPPOCAMPUS
No full textBackground: 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
VNS e Neuroplasticità
No full textLa stimolazione del nervo vago (VNS) è stata applicata con successo nel trattamento dell’epilessia resistente ai trattamenti farmacologici ed e stata successivamente approvata per il trattamento della depressione farmaco resistente. Fino ad oggi un numero considerevole di pazienti è stato trattato con la VNS, tuttavia, i meccanismi molecolari alla base dell’efficacia terapeutica della VNS non sono stati ancora chiariti. Osservazioni sperimentali hanno mostrato che la VNS potrebbe migliorare il tono dell’umore inducendo delle modificazioni dei ritmi cerebrali che passano attraverso il nucleo del tratto solitario (NTS), il principale nucleo sul quale terminano le fibre afferenti del nervo vago. Considerato l’estesissimo territorio di innervazione e le connessioni del NTS, la VNS probabilmente media i suoi effetti neurochimici ed elettrici attraverso diversi meccanismi. Questa evidenza neuroanatomica supporta l’idea che la VNS agisca stimolando i nuclei del tronco encefalico e indirettamente regolando l’attività neuronale delle regioni limbiche e corticali. Per chiarire i meccanismi molecolari alla base della putativa efficacia terapeutica della VNS nel trattamento della depressione farmaco resistente abbiamo utilizzato un modello animale, studiato le aree cerebrali coinvolte e gli eventi neurochimici e molecolari indotti dall’attivazione del NTS. La VNS nel ratto induce un aumento delle concentrazioni di noradrenalina nella corteccia prefrontale e un’induzione dell’espressione genica di fattori neurotrofici nella corteccia cerebrale e nell’ippocampo. La VNS induce proliferazione cellulare e neurogenesi nel giro dentato dell’ippocampo associata a una modificazione della citoarchitettura ippocampale e aumento delle arborizzazioni dendritiche dei neuroni del giro dentato dell’ippocampo. Questi effetti sono simili a quelli indotti dai farmaci antidepressivi, tuttavia non risultano essere associati positivamente ai classici test utilizzati normalmente per valutare l’attività antidepressiva dei farmaci
CHRONIC ETHANOL-MEDIATED UP-REGULATION OF THE N-METHYL-D-ASPARTATE RECEPTOR POLYPEPTIDE SUBUNITS IN MOUSE CORTICAL NEURONS IN CULTURE
No full textChronic ethanol treatment differentially regulates NMDA receptor subunit mRNA expression in rat brain
No full textRegulation of basic fibroblast growth factor and nerve growth factor mRNA by beta-adrenergic receptor activation and adrenal steroids in rat central nervous system
No full textNMDA receptor upregulation: molecular studies in cultured mouse cortical neurons after chronic antagonist exposure
No full textRegulation of NMDA receptor subunit mRNA expression following chronic exposure to antagonists and ethanol in vivo and in vitro
No full textEthanol-induced selective GABAA receptor gene expression changes: Possible role of brain steroidogenesis
No full textProlonged ethanol (EtOH) exposure has been shown to be associated to neuroadaptive changes that involve alterations of GABAA receptor (GABAAR) gene expression and function. We recently focused our attention to the effects of chronic EtOH exposure on the expression of the GABAAR delta subunit in different populations of cultured rat neurons. GABAARs containing delta subunit are extrasynaptic, mediate tonic inhibition, and show a preferential sensitivity for the agonist THIP as well as neurosteroids and low concentrations of EtOH. Long-term (5 days) EtOH exposure and withdrawal differently altered delta subunit mRNA and peptide levels in hippocampal neurons and cerebellar granule cells. These EtOH-induced changes in delta subunit expression were associated to significant alterations in the efficacy of THIP and allopregnanolone, as measured by patch clamp recordings. These results indicate that the expression of the GABAAR delta subunit undergoes marked changes following long-term EtOH exposure and this may result in important alterations in tonic GABAergic inhibitory activity as well as neuronal excitability. We also recently found that, in isolated rat hippocampal slices, acute exposure to EtOH results in the stimulation of local synthesis of neurosteroids which is also associated to a potentiation of the GABAAR function in CA1 pyramidal neurons. These effects appear to be independent from steroid precursors pro- duced by peripheral organs as they occur also in the hippocampus of adrenalectomized-castrated rats. These findings suggest that EtOH may modulate GABAAR function through an increase in de novo brain syn- thesis of neurosteroids that is independent from the stimulation of the HPA axis
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