الفهرس 
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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.