الفهرس | Only 14 pages are availabe for public view |
Abstract The current study aimed to explore the role of the SSRI, fluvoxamine, in protection against PTZ-induced hippocampal neurodegeneration and subsequent pathologic axonogenesis in mice. Further, the current study examined the possible involvement of 5-HT3 receptors in that putative neuroprotective effect of fluvoxamine. Pentylenetetrazol was employed to induce a model of chronic convulsions in mice. Mice showed an increase in seizure severity throughout the course of kindling. In addition PTZ-kindled mice showed hippocampal degeneration and high number darkly stained pycnotic cells in different hippocampal areas as indicated by H&E. Similarly, PTZtreated mice showed morphological alterations as well as hippocampal neuronal loss and atrophy as indicated by cresyl violet staining. Furthermore, PTZ-kindled mice showed greater hippocampal axonogenesis as indicated by high immunoreactivity to GAP-43. Moreover, repeated fluvoxamine (20 mg/kg) administration alleviated the seizure severity and reduced hippocampal neuronal loss in PTZ-kindled mice. Additionally, repeated administration of fluvoxamine trice weekly for a total of 13 dose prevented the signs of abnormal plasticity and downregulated signs of aberrant axonogenesis as evidenced by the reduction of expression of the GAP-43 protein. On the other hand, pretreatment with the selective 5-HT3 receptor blocker, ondansetron, before fluvoxamine therapy largely diminished the modulatory effect of fluvoxamine on seizure activity and hippocampal GAP-43 expression. As far as the role of 5-HT receptor subtypes in the modulation of seizure activity is concerned, the results are controversial. In conclusion, the present results provided evidence that activation of serotonergic signaling through activation of 5-HT3 receptors contributes to the antiseizure activity of fluvoxamine in PTZ-kindled mice. In addition, repeated fluvoxamine administration attenuates PTZinduced neuronal loss and prevents activation of neuroplasticity in the damaged hippocampus. These findings imply the therapeutic potential of SSRIs in pathologies associated with neurodegeneration and aberrant neuroplasticity. |